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Your search keyword '"deGruyter, Justine N."' showing total 3 results
Start Over Author "deGruyter, Justine N." Topic phosphorothioate oligonucleotides
3 results on '"deGruyter, Justine N."'

1. Unlocking P(V): Reagents for chiral phosphorothioate synthesis.

Author

Knouse KW, deGruyter JN, Schmidt MA, Zheng B, Vantourout JC, Kingston C, Mercer SE, Mcdonald IM, Olson RE, Zhu Y, Hang C, Zhu J, Yuan C, Wang Q, Park P, Eastgate MD, and Baran PS

Subjects
Genetic Therapy, Isomerism, Phosphorothioate Oligonucleotides chemistry, Phosphorothioate Oligonucleotides therapeutic use, Sulfur chemistry, Nucleotides chemistry, Phosphorothioate Oligonucleotides chemical synthesis
Abstract

Phosphorothioate nucleotides have emerged as powerful pharmacological substitutes of their native phosphodiester analogs with important translational applications in antisense oligonucleotide (ASO) therapeutics and cyclic dinucleotide (CDN) synthesis. Stereocontrolled installation of this chiral motif has long been hampered by the systemic use of phosphorus(III) [P(III)]-based reagent systems as the sole practical means of oligonucleotide assembly. A fundamentally different approach is described herein: the invention of a P(V)-based reagent platform for programmable, traceless, diastereoselective phosphorus-sulfur incorporation. The power of this reagent system is demonstrated through the robust and stereocontrolled synthesis of various nucleotidic architectures, including ASOs and CDNs, via an efficient, inexpensive, and operationally simple protocol., (Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Published
2018
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2. Serine-Selective Bioconjugation

Author

Vantourout, Julien C, Adusumalli, Srinivasa Rao, Knouse, Kyle W, Flood, Dillon T, Ramirez, Antonio, Padial, Natalia M, Istrate, Alena, Maziarz, Katarzyna, DeGruyter, Justine N, Merchant, Rohan R, Qiao, Jennifer X, Schmidt, Michael A, Deery, Michael J, Eastgate, Martin D, Dawson, Philip E, Bernardes, Gonçalo JL, and Baran, Phil S

Subjects
Models, Molecular, Binding Sites, Protein Conformation, Ubiquitin, Serine, Phosphorothioate Oligonucleotides, Amino Acid Sequence, Amino Acids, Phosphorylation, Peptides, Oxidation-Reduction, 3. Good health
Abstract

This Communication reports the first general method for rapid, chemoselective, and modular functionalization of serine residues in native polypeptides, which uses a reagent platform based on the P(V) oxidation state. This redox-economical approach can be used to append nearly any kind of cargo onto serine, generating a stable, benign, and hydrophilic phosphorothioate linkage. The method tolerates all other known nucleophilic functional groups of naturally occurring proteinogenic amino acids. A variety of applications can be envisaged by this expansion of the toolbox of site-selective bioconjugation methods.

3. Serine-Selective Bioconjugation

Author

Antonio Ramirez, Dillon T. Flood, Gonçalo J. L. Bernardes, Martin D. Eastgate, Katarzyna Maziarz, Rohan R. Merchant, Jennifer X. Qiao, Julien C. Vantourout, Alena Istrate, Justine N. deGruyter, Michael A. Schmidt, Srinivasa Rao Adusumalli, Natalia M. Padial, Kyle W. Knouse, Philip E. Dawson, Michael J. Deery, Phil S. Baran, Repositório da Universidade de Lisboa, Vantourout, Julien C [0000-0002-0602-069X], Knouse, Kyle W [0000-0001-9688-0513], Flood, Dillon T [0000-0002-6600-0287], Ramirez, Antonio [0000-0003-2636-6855], Padial, Natalia M [0000-0001-6067-3360], deGruyter, Justine N [0000-0003-0465-8988], Merchant, Rohan R [0000-0002-5472-8780], Schmidt, Michael A [0000-0002-4880-2083], Eastgate, Martin D [0000-0002-6487-3121], Dawson, Philip E [0000-0002-2538-603X], Bernardes, Gonçalo JL [0000-0001-6594-8917], Baran, Phil S [0000-0001-9193-9053], and Apollo - University of Cambridge Repository

Subjects
Models, Molecular, Protein Conformation, Phosphorothioate Oligonucleotides, Peptides and proteins, 010402 general chemistry, 01 natural sciences, Biochemistry, Article, Catalysis, Serine, chemistry.chemical_compound, Colloid and Surface Chemistry, Protein structure, Nucleophile, Selectivity, Amino Acid Sequence, Amino Acids, Phosphorylation, Functionalization, Peptide sequence, chemistry.chemical_classification, Binding Sites, Reagents, Bioconjugation, Ubiquitin, Monomers, General Chemistry, Combinatorial chemistry, 3. Good health, 0104 chemical sciences, Amino acid, Monomer, chemistry, Reagent, Peptides, Oxidation-Reduction
Abstract

Copyright © 2020 American Chemical Society, This Communication reports the first general method for rapid, chemoselective, and modular functionalization of serine residues in native polypeptides, which uses a reagent platform based on the P(V) oxidation state. This redox-economical approach can be used to append nearly any kind of cargo onto serine, generating a stable, benign, and hydrophilic phosphorothioate linkage. The method tolerates all other known nucleophilic functional groups of naturally occurring proteinogenic amino acids. A variety of applications can be envisaged by this expansion of the toolbox of site-selective bioconjugation methods., Financial support for this work was provided by Bristol-Myers Squibb, the NIH (GM-118176), the Marie Skłodowska-CurieGlobal Fellowships (749359-EnanSET to N.M.P) within the European Union’s Research and Innovation Framework Programme (2014−2020), FCT Portugal (IF/00624/2015), and the Royal Society (URF\R\180019). D.F. was supported by the National Center for Advancing Translational Sciences,National Institutes of Health, through Grant UL1 TR002551 and Linked Award TL1 TR002551.

Published
2020
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