124 results on '"Lutz JF"'
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2. PEG-based thermo-responsive polymer coatings for the control of cell adhesion
- Author
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Lankenau, A., primary, Wischerhoff, E., additional, Uhlig, K., additional, Börner, HG., additional, Lutz, JF., additional, and Duschl, C., additional
- Published
- 2009
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3. Das Medium der dritten Art: Sinnvolle Nutzung des Internet in der Anästhesie
- Author
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Krier C and Lutz Jf
- Subjects
Anesthesiology and Pain Medicine ,business.industry ,Anesthesia ,Emergency Medicine ,The Internet ,General Medicine ,Critical Care and Intensive Care Medicine ,business - Published
- 1998
4. Cu(0)-Mediated Controlled/Living Radical Polymerization: A Tool for Precise Multiblock Copolymer Synthesis
- Author
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Boyer, Cyrille, Whittaker, Michael R., Per Zetterlund, Lutz, Jf, Meyer, Ty, Ouchi, M., and Sawamoto, M.
5. Using ion mobility spectrometry to understand signal dilution during tandem mass spectrometry sequencing of digital polymers: Experimental evidence of intramolecular cyclization.
- Author
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Sergent I, Schutz T, Lutz JF, and Charles L
- Abstract
Rationale: Optimizing the structure of digital polymers is an efficient strategy to ensure their tandem mass spectrometry (MS/MS) readability. In block-truncated poly(phosphodiester)s, homolysis of C-ON bonds in long chains permits the release of smaller blocks amenable to sequencing. Yet the dissociation behavior of diradical blocks was observed to strongly depend on their charge state., Methods: Polymers were ionized in negative mode electrospray and activated in-source so that blocks released as primary fragments can be investigated using ion mobility spectrometry (IMS) or sequenced in the post-IMS collision cell. Collision cross sections (CCS) were derived from arrival times using a calibration procedure developed for polyanions using the IMSCal software. A multistep protocol based on quantum methods and classical molecular dynamics was implemented for molecular modeling and calculation of theoretical CCS., Results: Unlike their triply charged homologues, dissociation of diradical blocks at the 2- charge state produces additional fragments, with +1 m/z shift for those holding the nitroxide α-termination and -1 m/z for those containing the carbon-centered radical ω-end. These results suggest cyclization of these diradical species, followed by H
• transfer on activated reopening of this cycle. This assumption was validated using IMS resolution of the cyclic/linear isomers and supported by molecular modeling., Conclusions: Combining IMS with molecular modeling provided new insights into how the charge state of digital blocks influences their dissociation. These results permit to define new guidelines to improve either ionization conditions or the structural design of these digital polymers for best MS/MS readability., (© 2024 The Author(s). Rapid Communications in Mass Spectrometry published by John Wiley & Sons Ltd.)- Published
- 2024
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6. Complex Sequence-Defined Heteropolymers Enable Controlled Film Growth in Layer-By-Layer Assembly.
- Author
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Barman R, Tschopp M, Charles L, Decher G, Felix O, and Lutz JF
- Abstract
Digitally-encoded poly(phosphodiesters) (d-PPDE) with highly complex primary structures are evaluated for layer-by-layer (LbL) assembly. To be easily decoded by mass spectrometry (MS), these digital polymers contain many different monomers: 2 coding units allowing binary encryption, 1 cleavable spacer allowing controlled MS fragmentation, and 3 mass tags allowing fragment identification. These complex heteropolymers are therefore composed of 6 different motifs. Despite this strong sequence heterogeneity, it is found that they enable a highly controlled LbL film formation. For instance, a regular growth is observed when alternating the deposition of negatively-charged d-PPDE and positively-charged poly(allyl amine hydrochloride) (PAH). Yet, in this approach, the interdistance between consecutive coded d-PPDE layers remains relatively small, which may be an issue for data storage applications, especially for the selective decoding of the stored information. Using poly(sodium 4-styrene sulfonate) (PSS) as an intermediate non-coded polyanion, it is shown that a controlled interdistance between d-PPDE layers can be easily achieved, while still maintaining a regular LbL growth. Last but not least, it is found in this work that d-PPDE of relatively small molecular weight (i.e., significantly smaller than those of PAH and PSS) still enables a controlled LbL assembly., (© 2024 The Author(s). Macromolecular Rapid Communications published by Wiley‐VCH GmbH.)
- Published
- 2024
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7. Exchanging and Releasing Information in Synthetic Digital Polymers Using a Strand-Displacement Strategy.
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Nerantzaki M, Husser C, Ryckelynck M, and Lutz JF
- Subjects
- DNA, Single-Stranded, Recombination, Genetic, Organophosphates, DNA chemistry, Polymers
- Abstract
Toehold-mediated strand displacement (TMSD) was tested as a tool to edit information in synthetic digital polymers. Uniform DNA-polymer biohybrid macromolecules were first synthesized by automated phosphoramidite chemistry and characterized by HPLC, mass spectrometry, and polyacrylamide gel electrophoresis (PAGE). These precursors were diblock structures containing a synthetic poly(phosphodiester) (PPDE) segment covalently attached to a single-stranded DNA sequence. Three types of biohybrids were prepared herein: a substrate containing an accessible toehold as well as input and output macromolecules. The substrate and the input macromolecules contained noncoded PPDE homopolymers, whereas the output macromolecule contained a digitally encoded segment. After hybridization of the substrate with the output, incubation in the presence of the input led to efficient TMSD and the release of the digital segment. TMSD can therefore be used to erase or rewrite information in self-assembled biohybrid superstructures. Furthermore, it was found in this work that the conjugation of DNA single strands to synthetic segments of chosen lengths greatly facilitates the characterization and PAGE visualization of the TMSD process.
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- 2024
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8. Using Nitroxides To Model the Ion Mobility Behavior of Nitroxide-Ended Oligomers: A Bottom-up Approach To Predict Mobility Separation.
- Author
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Sergent I, Schutz T, Oswald L, Obeid G, Lutz JF, and Charles L
- Abstract
Block-truncated poly(phosphodiester)s are digital macromolecules storing binary information that can be decoded by MS/MS sequencing of individual blocks released as primary fragments of the entire polymer. As such, they are ideal species for the serial sequencing methodology enabled by MS-(CID)-IMS-(CID)-MS coupling, where two activation stages are combined in-line with ion mobility spectrometry (IMS) separation. Yet, implementation of this coupling still requires efforts to achieve IMS resolution of inner blocks, that can be considered as small oligomers with α termination composed of one nitroxide decorated with a different tag. As shown by molecular dynamics simulation, these oligomers adopt a conformation where the tag points out of the coil formed by the chain. Accordingly, the sole nitroxide termination was investigated here as a model to reduce the cost of calculation aimed at predicting the shift of collision cross-section (CCS) induced by new tag candidates and extrapolate this effect to nitroxide-terminated oligomers. A library of 10 nitroxides and 7 oligomers was used to validate our calculation methods by comparison with experimental IMS data as well as our working assumption. Based on conformation predicted by theoretical calculation, three new tag candidates could be proposed to achieve the +40 Å
2 CCS shift required to ensure IMS separation of oligomers regardless of their coded sequence.- Published
- 2024
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9. Conception and Evaluation of a Library of Cleavable Mass Tags for Digital Polymers Sequencing.
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Schutz T, Sergent I, Obeid G, Oswald L, Al Ouahabi A, Baxter PNW, Clément JL, Gigmes D, Charles L, and Lutz JF
- Abstract
A library of phosphoramidite monomers containing a main-chain cleavable alkoxyamine and a side-chain substituent of variable molar mass (i.e. mass tag) was prepared in this work. These monomers can be used in automated solid-phase phosphoramidite chemistry and therefore incorporated periodically as spacers inside digitally-encoded poly(phosphodiester) chains. Consequently, the formed polymers contain tagged cleavable sites that guide their fragmentation in mass spectrometry sequencing and enhance their digital readability. The spacers were all prepared via a seven steps synthetic procedure. They were afterwards tested for the synthesis and sequencing of model digital polymers. Uniform digitally-encoded polymers were obtained as major species in all cases, even though some minor defects were sometimes detected. Furthermore, the polymers were decoded in pseudo-MS
3 conditions, thus confirming the reliability and versatility of the spacers library., (© 2023 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)- Published
- 2023
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10. Macromolecular Information Transfer.
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Samokhvalova S and Lutz JF
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- Macromolecular Substances, DNA Replication, RNA, DNA genetics, Polymers
- Abstract
Macromolecular information transfer can be defined as the process by which a coded monomer sequence is communicated from one macromolecule to another. In such a transfer process, the information sequence can be kept identical, transformed into a complementary sequence or even translated into a different molecular language. Such mechanisms are crucial in biology and take place in DNA→DNA replication, DNA→RNA transcription and RNA→protein translation. In fact, there would be no life on Earth without macromolecular information transfer. Mimicking such processes with synthetic macromolecules would also be of major scientific relevance because it would open up new avenues for technological applications (e.g. data storage and processing) but also for the creation of artificial life. In this important context, this minireview summarizes recent research about information transfer in synthetic oligomers and polymers. Medium- and long-term perspectives are also discussed., (© 2023 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)
- Published
- 2023
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11. Covalent Attachment and Detachment by Reactive DESI of Sequence-Coded Polymer Taggants.
- Author
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Youssef I, Carvin-Sergent I, Konishcheva E, Kebe S, Greff V, Karamessini D, Matloubi M, Ouahabi AA, Moesslein J, Amalian JA, Poyer S, Charles L, and Lutz JF
- Subjects
- Disulfides chemistry, Hydrogels chemistry, Polyurethanes, Acrylamide, Spectrometry, Mass, Electrospray Ionization methods, Polymers, Acrylamides
- Abstract
The use of sequence-defined polymers is an interesting emerging solution for materials identification and traceability. Indeed, a very large amount of identification sequences can be created using a limited alphabet of coded monomers. However, in all reported studies, sequence-defined taggants are usually included in a host material by noncovalent adsorption or entrapment, which may lead to leakage, aggregation, or degradation. To avoid these problems, sequence-defined polymers are covalently attached in the present work to the mesh of model materials, namely acrylamide hydrogels. To do so, sequence-coded polyurethanes containing a disulfide linker and a terminal methacrylamide moiety are synthesized by stepwise solid-phase synthesis. These methacrylamide macromonomers are afterward copolymerized with acrylamide and bisacrylamide in order to achieve cross-linked hydrogels containing covalently-bound polyurethane taggants. It is shown herein that these taggants can be selectively detached from the hydrogel mesh by reactive desorption electrospray ionization. Using dithiothreitol the disulfide linker that links the taggant to the gel can be selectively cleaved. Ultimately, the released taggants can be decoded by tandem mass spectrometry., (© 2022 The Authors. Macromolecular Rapid Communications published by Wiley-VCH GmbH.)
- Published
- 2022
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12. Precisely Defined Aptamer- b -Poly(phosphodiester) Conjugates Prepared by Phosphoramidite Polymer Chemistry.
- Author
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Loth C, Charles L, Lutz JF, and Nerantzaki M
- Subjects
- Chromatography, High Pressure Liquid, Organophosphates, Organophosphorus Compounds, Aptamers, Nucleotide chemistry, Polymers chemistry
- Abstract
Uniform conjugates combining a DNA aptamer (either anti-MUC1 or ATP aptamer) and a synthetic polymer segment were synthesized by automated phosphoramidite chemistry. This multistep growth polymer chemistry enables the use of both natural (i.e., nucleoside phosphoramidites) and non-natural monomers (e.g., alkyl- and oligo(ethylene glycol)-phosphoramidites). Thus, in the present work, six different aptamer-polymer conjugates were synthesized and characterized by ion-exchange HPLC, circular dichroism spectroscopy, and electrospray mass spectrometry. All these methods evidenced the formation of uniform molecules with precisely controlled chain-length and monomer sequences. Furthermore, aptamer folding was not affected by polymer bioconjugation. The method described herein is straightforward and allows covalent attachment of homopolymers and copolymers to biofunctional DNA aptamers.
- Published
- 2021
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13. Design of Abiological Digital Poly(phosphodiester)s.
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Charles L and Lutz JF
- Abstract
In biological systems, the storage and transfer of genetic information rely on sequence-controlled nucleic acids such as DNA and RNA. It has been realized for quite some time that this property is not only crucial for life but could also be very useful in human applications. For instance, DNA has been actively investigated as a digital storage medium over the past decade. Indeed, the "hard-disk of life" is an obvious choice and a highly optimized material for storing data. Through decades of nucleic acids research, technological tools for parallel synthesis and sequencing of DNA have been readily available. Consequently, it has already been demonstrated that different types of documents (e.g., texts, images, videos, and industrial data) can be stored in chemically synthesized DNA libraries. However, DNA is subject to biological constraints, and its molecular structure cannot be easily varied to match technological needs. In fact, DNA is not the only macromolecule that enables data storage. In recent years, it has been demonstrated that a wide variety of synthetic polymers can also be used for such a purpose. Indeed, modern polymer synthesis allows the preparation of synthetic macromolecules with precisely controlled monomer sequences. Altogether, about a dozens of synthetic digital polymers have already been described, and many more can be foreseen. Among them, sequence-defined poly(phosphodiester)s are one of the most promising options. These polymers are prepared by stepwise phosphoramidite chemistry like chemically synthesized oligonucleotides. However, they are constructed with non-natural building blocks and therefore share almost no structural characteristics with nucleic acids, except phosphate repeat units. Still, they contain readable digital messages that can be deciphered by nanopore sequencing or mass spectrometry sequencing. In this Account, we describe our recent research efforts in synthesizing and sequencing optimal abiological digital poly(phosphodiester)s. A major advantage of these polymers over DNA is that their molecular structure can easily be varied to tune their properties. During the last 5 years, we have engineered the molecular structure of these polymers to adjust crucial parameters such as the storage density, storage capacity, erasability, and readability. Consequently, high-capacity PPDE chains, containing hundreds of bits per chains, can now be synthesized and efficiently sequenced using a routine mass spectrometer. Furthermore, sequencing data can be automatically decrypted with the help of decoding software. This new type of coded matter can also be edited using practical physical triggers such as light and organized in space by programmed self-assembly. All of these recent improvements are summarized and discussed herein.
- Published
- 2021
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14. Chain Entropy Beats Hydrogen Bonds to Unfold and Thread Dialcohol Phosphates inside Cyanostar Macrocycles To Form [3]Pseudorotaxanes.
- Author
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Fadler RE, Al Ouahabi A, Qiao B, Carta V, König NF, Gao X, Zhao W, Zhang Y, Lutz JF, and Flood AH
- Subjects
- Entropy, Hydrogen Bonding, Molecular Conformation, Phosphates, Rotaxanes
- Abstract
The recognition of substituted phosphates underpins many processes including DNA binding, enantioselective catalysis, and recently template-directed rotaxane synthesis. Beyond ATP and a few commercial substrates, however, little is known about how substituents effect organophosphate recognition. Here, we examined alcohol substituents and their impact on recognition by cyanostar macrocycles. The organophosphates were disubstituted by alcohols of various chain lengths, dipropanol, dihexanol, and didecanol phosphate, each accessed using modular solid-phases syntheses. Based on the known size-selective binding of phosphates by π-stacked dimers of cyanostars, threaded [3]pseudorotaxanes were anticipated. While seen with butyl substituents, pseudorotaxane formation was disrupted by competitive OH···O
- hydrogen bonding between both terminal hydroxyls and the anionic phosphate unit. Crystallography also showed formation of a backfolded propanol conformation resulting in an 8-membered ring and a perched cyanostar assembly. Motivated by established entropic penalties accompanying ring formation, we reinstated [3]pseudorotaxanes by extending the size of the substituent to hexanol and decanol. Chain entropy overcomes the enthalpically favored OH···O- contacts to favor random-coil conformations required for seamless, high-fidelity threading of dihexanol and didecanol phosphates inside cyanostars. These studies highlight how chain length and functional groups on phosphate's substituents can be powerful design tools to regulate binding and control assembly formation during phosphate recognition.- Published
- 2021
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15. Precise Alkoxyamine Design to Enable Automated Tandem Mass Spectrometry Sequencing of Digital Poly(phosphodiester)s.
- Author
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Launay K, Amalian JA, Laurent E, Oswald L, Al Ouahabi A, Burel A, Dufour F, Carapito C, Clément JL, Lutz JF, Charles L, and Gigmes D
- Abstract
A major step towards reliable reading of information coded in the sequence of long poly(phosphodiester)s was previously achieved by introducing an alkoxyamine spacer between information sub-segments. However, MS/MS decoding had to be performed manually to safely identify useful fragments of low abundance compared to side-products from the amide-based alkoxyamine used. Here, alternative alkoxyamines were designed to prevent side-reactions and enable automated MS/MS sequencing. Different styryl-TEMPO spacers were prepared to increase radical delocalization and stiffness of the structure. Their dissociation behavior was investigated by EPR and best results were obtained with spacers containing in-chain benzyl ring, with no side-reaction during synthesis or sequencing. Automated decoding of these polymers was performed using the MS-DECODER software, which interprets fragmentation data recorded for each sub-segment and re-align them in their original order based on location tags., (© 2020 Wiley-VCH GmbH.)
- Published
- 2021
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16. Aerolysin nanopores decode digital information stored in tailored macromolecular analytes.
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Cao C, Krapp LF, Al Ouahabi A, König NF, Cirauqui N, Radenovic A, Lutz JF, and Peraro MD
- Abstract
Digital data storage is a growing need for our society and finding alternative solutions than those based on silicon or magnetic tapes is a challenge in the era of "big data." The recent development of polymers that can store information at the molecular level has opened up new opportunities for ultrahigh density data storage, long-term archival, anticounterfeiting systems, and molecular cryptography. However, synthetic informational polymers are so far only deciphered by tandem mass spectrometry. In comparison, nanopore technology can be faster, cheaper, nondestructive and provide detection at the single-molecule level; moreover, it can be massively parallelized and miniaturized in portable devices. Here, we demonstrate the ability of engineered aerolysin nanopores to accurately read, with single-bit resolution, the digital information encoded in tailored informational polymers alone and in mixed samples, without compromising information density. These findings open promising possibilities to develop writing-reading technologies to process digital data using a biological-inspired platform., (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).)
- Published
- 2020
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17. Damage and Repair in Informational Poly(N-substituted urethane)s.
- Author
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Mondal T, Charles L, and Lutz JF
- Abstract
The degradation and repair of uniform sequence-defined poly(N-substituted urethane)s was studied. Polymers containing an ω-OH end-group and only ethyl carbamate main-chain repeat units rapidly degrade in NaOH solution through an ω→α depolymerization mechanism with no apparent sign of random chain cleavage. The degradation mechanism is not notably affected by the nature of the side-chain N-substituents and took place for all studied sequences. On the other hand, depolymerization is significantly influenced by the molecular structure of the main-chain repeat units. For instance, hexyl carbamate main-chain motifs block unzipping and can therefore be used to control the degradation of specific sequence sections. Interestingly, the partially degraded polymers can also be repaired; for example by using a combination of N,N'-disuccinimidyl carbonate with a secondary amine building-block. Overall, these findings open up interesting new avenues for chain-healing and sequence editing., (© 2020 Wiley-VCH GmbH.)
- Published
- 2020
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18. Optimal conditions for tandem mass spectrometric sequencing of information-containing nitrogen-substituted polyurethanes.
- Author
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Charles L, Mondal T, Greff V, Razzini M, Monnier V, Burel A, Carapito C, and Lutz JF
- Abstract
Rationale: To prevent solubility issues faced with sequence-defined polyurethanes, a new family of digital polyurethanes was conceived with the alkyl coding chain held by the carbamate nitrogen (N) atom and CH
3 instead of OH as the ϖ termination. This led to different dissociation mechanisms that were explored prior to optimizing tandem mass spectrometric (MS/MS) sequencing., Methods: N-Substituted polyurethanes (N-R PUs) were dissolved in methanol and subjected to collision-induced dissociation (CID) as deprotonated chains in the negative ion mode, and as ammonium and sodium adducts in the positive ion mode, using electrospray ionization (ESI) as the ionization technique. Their dissociation behavior was thoroughly investigated using a quadrupole time-of-flight (QTOF) instrument in order to provide accurate mass measurements to support proposed fragmentation mechanisms., Results: While O-(CO) bonds were broken in N-H PUs, the CH2 -O linkage between repeating units was cleaved upon CID of N-R PUs. This main process occurred either from deprotonated molecules or from cationized chains but was followed by different rearrangements, producing up to four product ion series. Yet, MS/MS spectra could be drastically simplified for precursor ions having their acidic α group methylated, as was found to spontaneously occur upon storage in methanol., Conclusions: Using experimental conditions aimed at avoiding any reactive proton in precursor ions (no acidic end-groups and alkali adduction), full coverage sequence of N-R PUs was successfully achieved with the single ion series observed in MS/MS, opening a promising perspective for reading large amounts of information stored in these dyad-encoded polymers., (© 2020 John Wiley & Sons, Ltd.)- Published
- 2020
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19. Selective Bond Cleavage in Informational Poly(Alkoxyamine Phosphodiester)s.
- Author
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Cavallo G, Clément JL, Gigmes D, Charles L, and Lutz JF
- Subjects
- Molecular Structure, Amines chemistry, Organophosphates chemistry, Polymers chemistry
- Abstract
The collision-induced dissociation (CID) of sequence-defined poly(alkoxyamine phosphodiester)s is studied by electrospray ionization mass spectrometry. These informational polymers are synthesized using three different nitroxide building blocks, namely proxyl-, SG1-, and TEMPO-derivatives. For a polymer containing TEMPO- and SG1-based main chain alkoxyamines, it is found that both types of alkoxyamines break in CID tandem mass spectrometry (MS/MS). However, SG1-sites are preferentially cleaved and this predominance can be increased by reducing collision energy, even though selective bond fragmentation is not observed. On the other hand, for a polymer containing proxyl- and SG1-alkoxyamines, selective bond cleavage is observed at all studied collision energies. The SG1-alkoxyamines can be first cleaved in MS/MS conditions and secondly the proxyl-alkoxyamines in pseudo-MS
3 conditions. These results open up interesting new avenues for the design of readable, erasable or programmable informational polymers., (© 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)- Published
- 2020
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20. 100th Anniversary of Macromolecular Science Viewpoint: Toward Artificial Life-Supporting Macromolecules.
- Author
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Lutz JF
- Abstract
Terrestrial Life is based on polymers. In all known living organisms, DNA stores genetic information, mutates, self-replicates, and guides the synthesis of messenger molecules. Although the function of nucleic acids is well-understood, the development of artificial macromolecular mimics remains very limited. Laboratory-synthesized nucleic acids still support Life, and some nucleic acids analogues exhibit biological functions. Yet, after hundred years of polymer science, no other type of Life-supporting macromolecule (i.e., non-nucleic acids) has ever been reported. In this context, the aim of the present viewpoint is to discuss important challenges that shall be addressed by polymer chemists to achieve artificial Life. Similarly to DNA, an artificial Life-supporting macromolecule shall store information, transfer information, and mutate. Many tools, such as sequence-defined polymer synthesis, polymer modification, supramolecular polymer chemistry, and dynamic chemistry, are already available to chemists to attain these properties. However, the design of artificial Life-supporting macromolecules is hindered by two main factors. First, the chemical search space is enormous, and it is difficult to predict promising structures, even with the help of combinatorial and chemoinformatic tools. Second, rational design is probably a limited approach to achieve macromolecules that shall be involved in nonequilibrium metabolic systems. Hence, a synergic combination of classical polymer chemistry with the more recent field of systems chemistry is probably the key toward the emergence of artificial Life-supporting macromolecules.
- Published
- 2020
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21. Photo-editable macromolecular information.
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König NF, Al Ouahabi A, Oswald L, Szweda R, Charles L, and Lutz JF
- Subjects
- Molecular Structure, Polymers chemical synthesis, Tandem Mass Spectrometry, Chemistry Techniques, Synthetic methods, Polymers radiation effects, Ultraviolet Rays
- Abstract
Light-induced alteration of macromolecular information plays a central role in biology and is known to influence health, aging and Darwinian evolution. Here, we report that light can also trigger sequence variations in abiotic information-containing polymers. Sequence-coded poly(phosphodiester)s were synthesized using four phosphoramidite monomers containing either photo-sensitive or photo-inert substituents. These monomers allow different sequence manipulations. For instance, using two light-cleavable monomers containing o-nitrobenzyl ether and o-nitroveratryl ether motifs, photo-erasable digital polymers were prepared. These polymers can be decoded by tandem mass spectrometry but become unreadable after UVA exposure. The opposite behavior, i.e. photo-revealable sequences, was obtained with polymers made of two isobaric monomers containing light-cleavable o-nitrobenzyl ether and light-inert p-nitrobenzyl ether substituents. Furthermore, when the latter two monomers were used in conjunction with a third monomer bearing a light-inert OH group, site-directed photo-mutations were induced in synthetic polymers. This was used herein to change the meaning of binary sequences.
- Published
- 2019
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22. Efficient Protocol for the Synthesis of " N -Coded" Oligo- and Poly( N -Substituted Urethanes).
- Author
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Mondal T, Greff V, Petit BÉ, Charles L, and Lutz JF
- Abstract
Sequence-defined poly( N -substituted urethanes) were synthesized via a solid-phase iterative protocol including two successive orthogonal coupling steps: the formation of an activated carbonate and its chemoselective reaction with the secondary amine group of amino alcohol building blocks. This simple method was used to write binary information on the formed polymers using four-coded molecules, 2-(methylamino)ethanol, 2-(ethylamino)ethanol, 2-(propylamino)ethanol, and 2-(butylamino)ethanol, symbolizing binary dyads 00, 01, 10, and 11, respectively. The method is fast and allows synthesis of uniform oligomers and polymers with controlled lengths (4-mer to 28-mer) and digital information sequences. Furthermore, the coded poly( N -substituted urethanes) were easily characterized by electrospray mass spectrometry and decoded by tandem mass spectrometry. Overall, these digital macromolecules offer interesting advantages over conventional sequence-coded polyurethanes, i.e., synthesis of longer chains, reduced synthesis times, and better solubility and processing in common organic solvents.
- Published
- 2019
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23. About the Crystallization of Abiotic Coded Matter.
- Author
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Petit BÉ, Lotz B, and Lutz JF
- Abstract
The crystallization of digitally encoded polyurethanes was studied by electron diffraction. A series of oligomers with different primary structures was analyzed in this work. They all form hydrogen-bonding-directed lamellar single crystals with a base-centered orthorhombic unit cell. Although crystal morphology was the same in all cases, the digital coding of the oligomers has a small influence on the intersheet distance in the crystals. The crystal lattices allow calculation of the volume occupied by one basic information unit, which is in the range 148-188 Å
3 . Interestingly, this volume is about 3× smaller than that occupied by a coded nucleotide in a DNA double helix. Furthermore, crystallization of blends of oligourethanes with different coded primary structures was investigated. Oligomers with drastically different monomer compositions form structures that are not cocrystals but more probably segregated crystals containing distinct domains of different composition.- Published
- 2019
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24. Revealing Data Encrypted in Sequence-Controlled Poly(Alkoxyamine Phosphodiester)s by Combining Ion Mobility with Tandem Mass Spectrometry.
- Author
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Amalian JA, Cavallo G, Al Ouahabi A, Lutz JF, and Charles L
- Abstract
The defined sequence of two comonomers in sequence-controlled macromolecules can be used to store binary information which is further decoded by MS/MS sequencing. In order to achieve the full sequence coverage requested for reliable decoding, the structure of these polymers can be optimized to minimize their dissociation extent, as shown for poly(alkoxyamine phosphodiester)s (PAPs) where weak alkoxyamine bonds were introduced in each repeating unit to make all phosphate groups MS/MS silent. However, for secret communications, a too high MS/MS readability could be a drawback. In this context, the design of PAPs was further optimized in this work to also include a decrypting key based on slight variation of a fragment collision cross section. This was achieved by employing two different nitroxides to build the alkoxyamine moiety, each containing a coding alkyl segment of the same mass but different architectures. As a result, the digital sequence determined from primary fragments observed in MS/MS had to be decrypted according to appropriate rules that depend on the drift times measured by ion mobility spectrometry for repeating units released as secondary product ions.
- Published
- 2019
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25. [The MDK community appraisal guideline for the German procedure classification code 8‑918 : Notification by the ad hoc commission for interdisciplinary multimodal pain therapy].
- Author
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Lutz JF, Böger A, and Arnold B
- Subjects
- Combined Modality Therapy, Germany, Humans, Pain Management, Pain
- Published
- 2018
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26. Sequences of Sequences: Spatial Organization of Coded Matter through Layer-by-Layer Assembly of Digital Polymers.
- Author
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Szweda R, Tschopp M, Felix O, Decher G, and Lutz JF
- Abstract
A library of 16 digitally encoded polyanions was used in a layer-by-layer (LbL) polyelectrolyte assembly to nanofabricate thin films containing digitally coded strata. The polyanions were digital polyphosphodiesters (d-PPDE) prepared via an automated phosphoramidite process. Each component of the library contained 10 bytes of ASCII-encoded text (i.e. 80 coded monomers); thus the entire library allows the writing of a full sentence, which can be stored in a multilayer film as a sequence of sequences. To prepare fully segregated digital domains, non-coded layers composed of poly(allylamine hydrochloride) (PAH)/poly(sodium 4-styrenesulfonate) (PSS) were included between the d-PPDE coded layers as an intermediate barrier. Detailed analysis of the film homogeneity indicated formation of 70 nm-thick films in which digital layers are kept apart from another by non-coded interlayers. As a result, the sequence-coded polymer library could be piled-up in a defined sequence of layers., (© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)
- Published
- 2018
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27. Abiotic Sequence-Coded Oligomers as Efficient In Vivo Taggants for the Identification of Implanted Materials.
- Author
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Karamessini D, Simon-Yarza T, Poyer S, Konishcheva E, Charles L, Letourneur D, and Lutz JF
- Subjects
- Abdomen pathology, Animals, Cell Line, Cell Survival drug effects, Humans, Methanol chemistry, Mice, Polyurethanes toxicity, Polyvinyl Alcohol analysis, Rats, Spectrometry, Mass, Electrospray Ionization, Polyurethanes chemistry, Polyvinyl Alcohol chemistry, Prostheses and Implants
- Abstract
Sequence-defined oligourethanes were tested as in vivo taggants for implant identification. The oligomers were prepared in an orthogonal solid-phase iterative approach and thus contained a coded monomer sequence that can be unequivocally identified by tandem mass spectrometry (MS/MS). The oligomers were then included in small amounts (1 wt %) in square-centimeter-sized crosslinked poly(vinyl alcohol) (PVA) model films, which were intramuscularly and subcutaneously implanted in the abdomen of rats. After one week, one month, or three months of implantation, the PVA films were explanted. The rat tissues exposed to the implants did not exhibit any adverse reactions, which suggested that the taggants are not harmful and probably not leaching out from the films. Furthermore, the explanted films were immersed in methanol, as a solvent for oligourethanes, and the liquid extract was analyzed by mass spectrometry. In all cases, the oligourethane taggant was detected, and its sequence was identified by MS/MS., (© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)
- Published
- 2018
- Full Text
- View/download PDF
28. Cleavable Binary Dyads: Simplifying Data Extraction and Increasing Storage Density in Digital Polymers.
- Author
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Cavallo G, Poyer S, Amalian JA, Dufour F, Burel A, Carapito C, Charles L, and Lutz JF
- Abstract
Digital polymers are uniform macromolecules that store monomer-based binary sequences. Molecularly stored information is usually extracted from the polymer by a tandem mass spectrometry (MS/MS) measurement, in which the coded chains are fragmented to reveal each bit (i.e. basic coded monomer unit) of the sequence. Here, we show that data-extraction can be greatly simplified by favoring the formation of MS/MS fragments containing two bits instead of one. In order to do so, digital poly(alkoxyamine phosphodiester)s, containing binary dyads in each repeat unit, were prepared by an orthogonal solid-phase approach involving successive phosphoramidite and radical-radical coupling steps. Three different sets of monomers were considered to build these polymers. In all cases, four coded building blocks-two hydroxy-nitroxides and two phosphoramidite monomers-were required to build the dyads. Among the three studied monomer sets, one combination allowed synthesis of uniform sequence-coded polymers. The resulting polymers led to clear dyad-containing fragments in MS/MS and could therefore be efficiently decoded. Additionally, an algorithm was created to detect specific dyad fragments, thus enabling automated sequencing., (© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)
- Published
- 2018
- Full Text
- View/download PDF
29. Synthesis of Macromolecules Containing Phenylalanine and Aliphatic Building Blocks.
- Author
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Chan-Seng D, Louwsma J, Lutz JF, and Joly S
- Subjects
- Hydrophobic and Hydrophilic Interactions, Macromolecular Substances chemistry, Materials Testing, Surface Properties, Phenylalanine chemistry, Polymers chemistry
- Abstract
Aiming at developing efficient interfacial agents for fiber-reinforced composite materials, macromolecules are designed to have different components able to stick to the fiber and be compatible with the polymer matrix, respectively. Herein, macromolecules are prepared by solid-phase synthesis considering phenylalanine residues to promote adsorption of the macromolecule on aramid fibers and aliphatic building blocks to interact with a hydrophobic polymer matrix. Using phenylalanine as building block for the preparation of macromolecules by iterative synthesis has been shown to be challenging. Thus, the screening of various parameters for the optimization of the synthesis of these macromolecules is discussed in this communication. A preliminary thermal study by thermal gravimetric analysis is conducted to evaluate their thermal stability., (© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)
- Published
- 2018
- Full Text
- View/download PDF
30. Translocation of Precision Polymers through Biological Nanopores.
- Author
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Boukhet M, König NF, Ouahabi AA, Baaken G, Lutz JF, and Behrends JC
- Subjects
- Entropy, Nanopores, Aeromonas hydrophila chemistry, Bacterial Toxins analysis, Hemolysin Proteins analysis, Organophosphates chemistry, Polymers chemistry, Pore Forming Cytotoxic Proteins analysis, Staphylococcus aureus chemistry
- Abstract
Nanopore analysis, which is, currently, chiefly used for DNA sequencing, is also an appealing technique for characterizing abiotic polymers. As a first step toward this goal, nanopore detection of non-natural monodispersed poly(phosphodiester)s as candidate backbone structures is reported herein. Two model homopolymers containing phosphopropyl repeat units (i.e., 56 or 104 r.u.) and a short thymidine nucleotide sequence are analyzed in the present work. They are tested in two different biological nanopores, α-hemolysin from Staphylococcus aureus, and aerolysin from Aeromonas hydrophila. These recordings are performed in aqueous medium at different KCl concentrations and various driving voltages. The data show a complex interaction with evidence for voltage dependence and threading, and underline the influence of the molecular structure and orientation of the precision poly(phosphodiester)s on the observed residual current signal as well as on the translocation dynamics. In particular, they suggest a dominant entropic contribution due to the high flexibility of the phosphodiester homopolymer., (© 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)
- Published
- 2017
- Full Text
- View/download PDF
31. Photocontrolled Synthesis of Abiotic Sequence-Defined Oligo(Phosphodiester)s.
- Author
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König NF, Telitel S, Poyer S, Charles L, and Lutz JF
- Subjects
- Molecular Structure, Organophosphates chemistry, Photochemical Processes, Organophosphates chemical synthesis
- Abstract
A photoregulated phosphoramidite iterative process is studied for the synthesis of non-natural, digitally encoded oligo(phosphodiester)s. The oligomers are prepared using two reactive phosphoramidite monomers containing a 2-(2-nitrophenyl)propoxycarbonyl (NPPOC) protected OH group. The stepwise synthesis is performed on an OH-functional soluble polystyrene support, which allows recycling by precipitation in a nonsolvent. Repeating cycles involving phosphoramidite coupling, oxidation of phosphite to phosphate, and NPPOC deprotection by light irradiation at λ = 365 nm are performed in order to prepare oligomers with different lengths and sequences. Synthesis is conducted on a micromolar scale and good recycling yields are obtained in all cases. The use of a soluble polymer support allows an in-depth characterization of the NPPOC photo-deprotection step by
1 H NMR, UV spectroscopy, and size exclusion chromatography, and thus identification of optimal synthesis conditions. After cleavage from the support, the oligo(phosphodiester)s are characterized by tandem mass spectrometry, which confirms preparation of uniform sequence-coded oligomers., (© 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)- Published
- 2017
- Full Text
- View/download PDF
32. [Interdisciplinary pain assessment in the hospital setting : Merely a door-opener to multimodal pain therapy?]
- Author
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Sens E, Mothes-Lasch M, and Lutz JF
- Subjects
- Combined Modality Therapy, Germany, Humans, Retrospective Studies, Pain Clinics, Pain Management, Pain Measurement
- Abstract
Background: Chronic pain is characterized by a complex interaction of somatic, mental and social factors. Assessing these factors in patients with chronic pain is vital during the diagnostic work-up and when making a structured treatment plan. Interdisciplinary pain assessment (ISA) is the most promising method to deal with these challenges. This article presents our experience in performing pain assessments in the hospital setting and also illustrates the characteristic features of chronic pain patients undergoing such assessments., Methods: This study reviews and evaluates patient data from 2704 ISAs performed at the Interdisciplinary Pain Centre of the Zentralklinik Bad Berka, Germany, between 2008 and 2015., Results: The majority of our ISA patients are severely handicapped and show distinct signs of chronic disease. A large proportion of patients is either unable to work or receiving benefits (invalidity pension or retirement pension). In addition, patients reported long disease durations and high emotional distress. Treatment recommendations were based on the patients' individual clinical presentations and examination results. More than half of the patients required multimodal pain management, while adjustments or therapeutic withdrawal of pain medications, in particular of opioids, were indicated in many patients., Discussion: Our study shows that ISA enables fast, high-quality diagnostic assessments of chronic pain while taking the biopsychosocial model of pain in particular into account. In addition, ISA is not biased with regard to outcome results and recommends the further treatment that appears best for the individual patient. ISA leads not only to inpatient treatment, but also to treatment in other therapeutic settings and, as such, is not merely a door-opener to multimodal pain therapy.
- Published
- 2017
- Full Text
- View/download PDF
33. 2D Sequence-Coded Oligourethane Barcodes for Plastic Materials Labeling.
- Author
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Karamessini D, Poyer S, Charles L, and Lutz JF
- Subjects
- Mass Spectrometry, Plastics chemical synthesis, Urethane chemical synthesis, Plastics chemistry, Polyethylene Terephthalates chemistry, Polystyrenes chemistry, Polyvinyl Chloride chemistry, Urethane chemistry
- Abstract
Mixtures of uniform sequence-defined oligourethanes are evaluated as 2D molecular barcodes for labeling three different commodity polymers, namely polystyrene, polyvinylchloride and polyethylene terephthalate. Six different oligourethanes are synthesized by solid-phase iterative synthesis and are coded using a binary monomer alphabet. High-resolution mass spectrometry studies indicate that all oligomers are uniform and sequence-defined. However, instead of using them as individual coded chains, oligomers with different chain-length, mass and sequence are mixed into intentionally polydispersed libraries. In particular, a three-component library and a four-component library are created to encode a 2-bytes model binary sequence. These 2D-coded libraries are incorporated in all commodity plastics via a simple solvent casting procedure. Furthermore, in all cases, the oligomer mixtures can be extracted from the host polymer films and deciphered by mass spectrometry, thus opening interesting avenues for anti-counterfeiting and traceability applications., (© 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)
- Published
- 2017
- Full Text
- View/download PDF
34. Defining the Field of Sequence-Controlled Polymers.
- Author
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Lutz JF
- Subjects
- Polymers chemistry, Polymers chemical synthesis
- Abstract
Over the last ten years, the development of synthetic polymers containing controlled monomer sequences has become a prominent topic in fundamental and applied polymer science. This emerging area is particularly broad and combines classical polymer chemistry tools with techniques imported from other domains such as biology, biochemistry, organic synthesis, engineering, and bioanalytics. Consequently, it also generates new structures, terminologies, and applications that are not within the traditional scope of polymer science. The term "sequence-controlled polymers" (SCPs) was recently proposed as a generic name to describe all these recent trends. However, since the field of SCPs has been growing very rapidly in recent literature, it is urgent to accurately define its scientific frontiers. In this important context, this review is an attempt to define, rationalize, and classify the field of SCPs. In particular, all synthetic approaches that have been reported for the synthesis of SCPs are discussed and categorized. In addition, the characterization tools, properties, and potential applications of these new polymers are described herein. Overall, this review serves as a reference guide for understanding the burgeoning field of SCPs., (© 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)
- Published
- 2017
- Full Text
- View/download PDF
35. Euro-Sequences: Toward Next-Gen Polymers.
- Author
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Lutz JF
- Subjects
- Europe, Macromolecular Substances chemical synthesis, Macromolecular Substances chemistry, Polymerization, Polymers chemistry, Polymers chemical synthesis
- Published
- 2017
- Full Text
- View/download PDF
36. Controlling the structure of sequence-defined poly(phosphodiester)s for optimal MS/MS reading of digital information.
- Author
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Amalian JA, Al Ouahabi A, Cavallo G, König NF, Poyer S, Lutz JF, and Charles L
- Abstract
Digital polymers are monodisperse chains with a controlled sequence of co-monomers, defined as letters of an alphabet, and are used to store information at the molecular level. Reading such messages is hence a sequencing task that can be efficiently achieved by tandem mass spectrometry. To improve their readability, structure of sequence-controlled synthetic polymers can be optimized, based on considerations regarding their fragmentation behavior. This strategy is described here for poly(phosphodiester)s, which were synthesized as monodisperse chains with more than 100 units but exhibited extremely complex dissociation spectra. In these polymers, two repeating units that differ by a simple H/CH
3 variation were defined as the 0 and 1 bit of the ASCII code and spaced by a phosphate moiety. They were readily ionized in negative ion mode electrospray but dissociated via cleavage at all phosphate bonds upon collisional activation. Although allowing a complete sequence coverage of digital poly(phosphodiester)s, this fragmentation behavior was not efficient for macromolecules with more than 50 co-monomers, and data interpretation was very tedious. The structure of these polymers was then modified by introducing alkoxyamine linkages at appropriate location throughout the chain. A first design consisted of placing these low dissociation energy bonds between each monomeric bit: while cleavage of this sole bond greatly simplified MS/MS spectra, efficient sequencing was limited to chains with up to about 50 units. In contrast, introduction of alkoxyamine bonds between each byte (i.e. a set of eight co-monomers) was a more successful strategy. Long messages (so far, up to 8 bytes) could be read in MS3 experiments, where single-byte containing fragments released during the first activation stage were further dissociated for sequencing. The whole sequence of such byte-truncated poly(phosphodiester)s could be easily re-constructed based on a mass tagging system which permits to determine the original location of each byte in the chain. Copyright © 2017 John Wiley & Sons, Ltd., (Copyright © 2017 John Wiley & Sons, Ltd.)- Published
- 2017
- Full Text
- View/download PDF
37. Mass spectrometry sequencing of long digital polymers facilitated by programmed inter-byte fragmentation.
- Author
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Al Ouahabi A, Amalian JA, Charles L, and Lutz JF
- Abstract
In the context of data storage miniaturization, it was recently shown that digital information can be stored in the monomer sequences of non-natural macromolecules. However, the sequencing of such digital polymers is currently limited to short chains. Here, we report that intact multi-byte digital polymers can be sequenced in a moderate resolution mass spectrometer and that full sequence coverage can be attained without requiring pre-analysis digestion or the help of sequence databases. In order to do so, the polymers are designed to undergo controlled fragmentations in collision-induced dissociation conditions. Each byte of the sequence is labeled by an identification tag and a weak alkoxyamine group is placed between 2 bytes. As a consequence of this design, the NO-C bonds break first upon collisional activation, thus leading to a pattern of mass tag-shifted intact bytes. Afterwards, each byte is individually sequenced in pseudo-MS
3 conditions and the whole sequence is found.Digital information can be stored in monomer sequences of non-natural macromolecules, but only short chains can be read. Here the authors show long multi-byte digital polymers sequenced in a moderate resolution mass spectrometer. Full sequence coverage can be attained without pre-analysis digestion or the help from sequence databases.- Published
- 2017
- Full Text
- View/download PDF
38. Synthesis of oligoarylacetylenes with defined conjugated sequences using tailor-made soluble polymer supports.
- Author
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Szweda R, Chendo C, Charles L, Baxter PNW, and Lutz JF
- Abstract
Due to their strong tendency to self-aggregate, unfunctionalized oligoarylacetylenes are difficult to synthesize. Here, tailored polystyrene soluble supports, prepared by atom transfer radical polymerization and post-polymerization modification, were tested for preparing sequence-defined oligoarylacetylenes. Controlled aromatic sequences were obtained by iterative Sonogarisha coupling, using phenyl- and pyridine-based building-blocks.
- Published
- 2017
- Full Text
- View/download PDF
39. A Simple Post-Polymerization Modification Method for Controlling Side-Chain Information in Digital Polymers.
- Author
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König NF, Al Ouahabi A, Poyer S, Charles L, and Lutz JF
- Abstract
A three-step post-polymerization modification method was developed for the design of digitally encoded poly(phosphodiester)s with controllable side groups. Sequence-defined precursors were synthesized, either manually on polystyrene resins or automatically on controlled pore glass supports, using two phosphoramidite monomers containing either terminal alkynes or triisopropylsilyl (TIPS) protected alkyne side groups. Afterwards, these polymers were modified by stepwise copper-catalyzed azide-alkyne cycloaddition (CuAAC). The terminal alkynes were first reacted with a model azide compound, and after removal of the TIPS groups, the remaining alkynes were reacted with another organic azide. This simple method allows for quantitative side-chain modification, thus opening up interesting avenues for the preparation of a wide variety of digital polymers., (© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)
- Published
- 2017
- Full Text
- View/download PDF
40. MS/MS-Assisted Design of Sequence-Controlled Synthetic Polymers for Improved Reading of Encoded Information.
- Author
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Charles L, Cavallo G, Monnier V, Oswald L, Szweda R, and Lutz JF
- Subjects
- Ion Mobility Spectrometry, Organophosphates chemistry, Polymers chemical synthesis, Triazoles chemistry, Polymers chemistry, Structure-Activity Relationship, Tandem Mass Spectrometry methods
- Abstract
In order to improve their MS/MS sequencing, structure of sequence-controlled synthetic polymers can be optimized based on considerations regarding their fragmentation behavior in collision-induced dissociation conditions, as demonstrated here for two digitally encoded polymer families. In poly(triazole amide)s, the main dissociation route proceeded via cleavage of the amide bond in each monomer, hence allowing the chains to be safely sequenced. However, a competitive cleavage of an ether bond in a tri(ethylene glycol) spacer placed between each coding moiety complicated MS/MS spectra while not bringing new structural information. Changing the tri(ethylene glycol) spacer to an alkyl group of the same size allowed this unwanted fragmentation pathway to be avoided, hence greatly simplifying the MS/MS reading step for such undecyl-based poly(triazole amide)s. In poly(alkoxyamine phosphodiester)s, a single dissociation pathway was achieved with repeating units containing an alkoxyamine linkage, which, by very low dissociation energy, made any other chemical bonds MS/MS-silent. Structure of these polymers was further tailored to enhance the stability of those precursor ions with a negatively charged phosphate group per monomer in order to improve their MS/MS readability. Increasing the size of both the alkyl coding moiety and the nitroxide spacer allowed sufficient distance between phosphate groups for all of them to be deprotonated simultaneously. Because the charge state of product ions increased with their polymerization degree, MS/MS spectra typically exhibited groups of fragments at one or the other side of the precursor ion depending on the original α or ω end-group they contain, allowing sequence reconstruction in a straightforward manner. Graphical Abstract ᅟ.
- Published
- 2017
- Full Text
- View/download PDF
41. Orthogonal Synthesis of Xeno Nucleic Acids.
- Author
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Fiers G, Chouikhi D, Oswald L, Al Ouahabi A, Chan-Seng D, Charles L, and Lutz JF
- Subjects
- Amino Acid Sequence, Catalysis, Cycloaddition Reaction, Nucleic Acids chemistry, Alkynes chemistry, Azides chemistry, Carboxylic Acids chemistry, Copper chemistry, Nucleic Acids chemical synthesis
- Abstract
Sequence-defined peptide triazole nucleic acids (PTzNA) were synthesized by means of a solid-phase orthogonal "AB+CD" iterative strategy. In this approach, AB and CD building blocks containing carboxylic acid (A), azide (B), alkyne (C), and primary amine (D) functions are assembled together by successive copper-catalyzed azide-alkyne cycloaddition (CuAAC) and acid-amine coupling steps. Different PTzNA genetic sequences were prepared using a library of eight building blocks (i.e., four AB and four CD building blocks)., (© 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)
- Published
- 2016
- Full Text
- View/download PDF
42. Coding in 2D: Using Intentional Dispersity to Enhance the Information Capacity of Sequence-Coded Polymer Barcodes.
- Author
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Laure C, Karamessini D, Milenkovic O, Charles L, and Lutz JF
- Abstract
A 2D approach was studied for the design of polymer-based molecular barcodes. Uniform oligo(alkoxyamine amide)s, containing a monomer-coded binary message, were synthesized by orthogonal solid-phase chemistry. Sets of oligomers with different chain-lengths were prepared. The physical mixture of these uniform oligomers leads to an intentional dispersity (1st dimension fingerprint), which is measured by electrospray mass spectrometry. Furthermore, the monomer sequence of each component of the mass distribution can be analyzed by tandem mass spectrometry (2nd dimension sequencing). By summing the sequence information of all components, a binary message can be read. A 4-bytes extended ASCII-coded message was written on a set of six uniform oligomers. Alternatively, a 3-bytes sequence was written on a set of five oligomers. In both cases, the coded binary information was recovered., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)
- Published
- 2016
- Full Text
- View/download PDF
43. Orthogonal Synthesis of "Easy-to-Read" Information-Containing Polymers Using Phosphoramidite and Radical Coupling Steps.
- Author
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Cavallo G, Al Ouahabi A, Oswald L, Charles L, and Lutz JF
- Abstract
A new orthogonal solid-phase iterative strategy is proposed for the synthesis of sequence-coded polymers. This approach relies on the use of two successive chemoselective steps: (i) phosphoramidite coupling, and (ii) radical-radical coupling. These repeated steps can be performed using two different types of building blocks, i.e. a phosphoramidite monomer that also contains an alkyl bromide and a hydroxy-functionalized nitroxide. The phosphoramidite and the hydroxy group are reacted in step (i), thus leading to a phosphite that is oxidized in situ into a phosphate bond. The alkyl bromide is activated by copper bromide in step (ii) to afford a carbon-centered radical that is spin-trapped in situ by the nitroxide. The iterative repetition of these steps allow synthesis of uniform polymers, as evidenced by high-resolution electrospray mass spectrometry. Moreover, binary information could be easily implemented in the polymers using different types of phosphoramidite monomers in step (i). Interestingly, it was found that the formed information-containing polymers are very easy to sequence by tandem mass spectrometry due to the presence of easily cleavable alkoxyamine bonds formed in step (ii).
- Published
- 2016
- Full Text
- View/download PDF
44. MS/MS Digital Readout: Analysis of Binary Information Encoded in the Monomer Sequences of Poly(triazole amide)s.
- Author
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Amalian JA, Trinh TT, Lutz JF, and Charles L
- Abstract
Tandem mass spectrometry was evaluated as a reliable sequencing methodology to read codes encrypted in monodisperse sequence-coded oligo(triazole amide)s. The studied oligomers were composed of monomers containing a triazole ring, a short ethylene oxide segment, and an amide group as well as a short alkyl chain (propyl or isobutyl) which defined the 0/1 molecular binary code. Using electrospray ionization, oligo(triazole amide)s were best ionized as protonated molecules and were observed to adopt a single charge state, suggesting that adducted protons were located on every other monomer unit. Upon collisional activation, cleavages of the amide bond and of one ether bond were observed to proceed in each monomer, yielding two sets of complementary product ions. Distribution of protons over the precursor structure was found to remain unchanged upon activation, allowing charge state to be anticipated for product ions in the four series and hence facilitating their assignment for a straightforward characterization of any encoded oligo(triazole amide)s.
- Published
- 2016
- Full Text
- View/download PDF
45. Optimal ATRP-Made Soluble Polymer Supports for Phosphoramidite Chemistry.
- Author
-
Oswald L, Al Ouahabi A, Charles L, and Lutz JF
- Abstract
Soluble polystyrene supports with optimal molecular structures for iterative phosphoramidite chemistry were prepared by atom-transfer radical polymerization (ATRP) and subsequent chain-end modification steps. The controlled radical polymerization of styrene was first performed in the presence of an 9-fluorenylmethoxycarbonyl (Fmoc)-protected amino-functional ATRP initiator. Soluble supports of different molecular weight were prepared. Size-exclusion chromatography and NMR analysis indicated formation of well-defined polymers with controlled chain lengths and narrow dispersity. After synthesis, the bromo ω end group of the ATRP polymer was removed by dehalogenation in the presence of tributyltin hydride, and the Fmoc protecting group of the α moiety was subsequently cleaved with piperidine. The resulting α-primary amine was afterwards treated with a linker containing a carboxyl group, a cleavable ester site, and a dimethoxytrityl-protected hydroxyl group to afford ideal soluble supports for phosphoramidite chemistry. NMR analysis indicated that these chain-end modifications were quantitative. The supports were tested for the synthesis of a non-natural sequence-defined oligophosphates. High-resolution ESI-MS analysis of the cleaved oligomers indicated formation of uniform species, and thus confirmed the efficiency of the ATRP-made soluble polymer supports. In addition, the synthesis of a thymidine-loaded soluble support was achieved., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)
- Published
- 2016
- Full Text
- View/download PDF
46. Tandem mass spectrometry sequencing in the negative ion mode to read binary information encoded in sequence-defined poly(alkoxyamine amide)s.
- Author
-
Charles L, Laure C, Lutz JF, and Roy RK
- Abstract
Rationale: Digitally encoded oligomers composed of two distinct amide coding units spaced by a nitroxide moiety were recently decrypted using a tandem mass spectrometry (MS/MS) sequencing approach developed for protonated oligomers. Here, the MS/MS behavior of deprotonated oligomers was explored in the negative ion mode to provide both structural and mechanistic complementary information., Methods: Binary-encoded oligo(alkoxyamine)amides, containing coding 0/1 amide units spaced by a TEMPO nitroxide moiety, were ionized in negative ion mode electrospray thanks to their α end-group containing a carboxylic acid function. Deprotonated molecules were subjected to collision-induced dissociation in MS/MS and MS(3) experiments, combined with accurate mass measurements, for a thorough investigation of their dissociation behavior., Results: Deprotonated oligomers readily dissociated upon collisional activation via competitive homolytic cleavages of all fragile alkoxyamine linkages between any coding 0 or 1 monomers and a nitroxide moiety. As expected, only product ions holding the deprotonated α end-group were detected while complementary moieties containing the ω termination were released as radicals. The so-formed distonic radical anions were observed to further depolymerize according to a radical-induced process, as evidenced by MS(3) experiments., Conclusions: Messages encoded in oligo(alkoxyamine)amides were readily decrypted by MS/MS sequencing performed in the negative ion mode. When compared with results obtained in positive ion mode ESI-MS/MS, these data provided further evidence regarding the influence of adducted proton on the charge-remote homolytic cleavage of alkoxyamine linkages., (Copyright © 2015 John Wiley & Sons, Ltd.)
- Published
- 2016
- Full Text
- View/download PDF
47. Convergent synthesis of digitally-encoded poly(alkoxyamine amide)s.
- Author
-
Roy RK, Laure C, Fischer-Krauser D, Charles L, and Lutz JF
- Abstract
Binary-encoded poly(alkoxyamine amide)s were prepared by oligomer ligation. These polymers contain digital sequences based on two monomers defined as 0 and 1 bits. A library of oligomers containing all possible dyads 00, 01, 10 and 11 was prepared and used to construct long coded sequences.
- Published
- 2015
- Full Text
- View/download PDF
48. Synthesis of Monodisperse Sequence-Coded Polymers with Chain Lengths above DP100.
- Author
-
Al Ouahabi A, Kotera M, Charles L, and Lutz JF
- Abstract
Non-natural, sequence-encoded polyphosphates were prepared using the phosphoramidite approach on a DNA synthesizer. Two phosphoramidite monomers, namely, 2-cyanoethyl (3-dimethoxytrityloxy-propyl) diisopropylphosphoramidite ( 0 ) and 2-cyanoethyl (3-dimethoxytrityloxy-2,2-dimethyl-propyl) diisopropylphosphoramidite ( 1 ), were used in this approach to form binary-coded sequences. Using 1000 Å controlled pore glass as a support and a large excess of monomers at each step, it was possible to synthesize homopolymers and sequence-coded copolymers of high chain-length. For instance, monodisperse polymers containing 16, 24, 56, and 104 coded monomer units were synthesized and characterized in this work. These results indicate that highly efficient phosphoramidite steps are suitable for the synthesis of long non-natural information-containing macromolecules.
- Published
- 2015
- Full Text
- View/download PDF
49. Preparation of Information-Containing Macromolecules by Ligation of Dyad-Encoded Oligomers.
- Author
-
Trinh TT, Oswald L, Chan-Seng D, Charles L, and Lutz JF
- Abstract
A simplified strategy for preparing non-natural information-containing polymers is reported. The concept relies on the successive ligation of oligomers that contain minimal sequence motifs. It was applied here to the synthesis of digitally-encoded poly(triazole amide)s, in which propyl and 2-methyl propyl motifs are used to code 0 and 1, respectively. A library of four oligo(triazole amide)s containing the information dyads 00, 01, 10, and 11 was prepared. These oligomers contain two reactive functions, that is, an alkyne and a carboxylic acid. Thus, they can be linked to another with the help of a reactive spacer containing azide and amine functions. Using two successive chemoselective steps, that is, azide-alkyne Huisgen cycloaddition and carboxylic acid-amine coupling, monodisperse polymers can be obtained. In particular, the library of dyads permits the implementation of any desired sequence using a small number of steps. As a proof-of-concept, the synthesis of molecular bytes 00000000 and 00000110 is described., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)
- Published
- 2015
- Full Text
- View/download PDF
50. Design and synthesis of digitally encoded polymers that can be decoded and erased.
- Author
-
Roy RK, Meszynska A, Laure C, Charles L, Verchin C, and Lutz JF
- Abstract
Biopolymers such as DNA store information in their chains using controlled sequences of monomers. Here we describe a non-natural information-containing macromolecule that can store and retrieve digital information. Monodisperse sequence-encoded poly(alkoxyamine amide)s were synthesized using an iterative strategy employing two chemoselective steps: the reaction of a primary amine with an acid anhydride and the radical coupling of a carbon-centred radical with a nitroxide. A binary code was implemented in the polymer chains using three monomers: one nitroxide spacer and two interchangeable anhydrides defined as 0-bit and 1-bit. This methodology allows encryption of any desired sequence in the chains. Moreover, the formed sequences are easy to decode using tandem mass spectrometry. Indeed, these polymers follow predictable fragmentation pathways that can be easily deciphered. Moreover, poly(alkoxyamine amide)s are thermolabile. Thus, the digital information encrypted in the chains can be erased by heating the polymers in the solid state or in solution.
- Published
- 2015
- Full Text
- View/download PDF
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