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Cellulose is a biodegradable and renewable material that is one of the most abundant biopolymers with many different applications from low value newsprint products to high value biomedical sensor devices. In the last years, the demand of functionalized cellulose for the development of new packaging materials was constantly rising. In this study, a new two-step method for surface functionalization of cellulose sheets and fibers involving oxidation by 2,2,6,6-tetramethylpiperidinyloxyl (TEMPO) followed by coupling of different proteins was investigated. The cellulose oxidation was monitored via FT-IR at 1610 cm−1, photometrically via toluidine blue staining and via titration for the determination of the –COOH group concentration. TEMPO oxidation increased the amount of –COOH groups from around 0.2 to more than 1.4 mmol g−1 when NaClO2/NaClO regeneration was used. The TEMPO/laccase system instead led to 0.7 mmol g−1 of –COOH groups (determined via HCl titration). The oxidation was monitored over time and showed that 50% of the reaction were completed within the first 60 min of reaction time. Coupling of protein-based hydrophobins or bovine serum albumin using the EDAC/NHS system led to the desired increase in hydrophobicity and detection of protein on cellulose. Coupling was investigated using contact angle measurements and SEM microscopy paired with elemental analysis for oxygen and nitrogen. Hence, the coupled hydrophobins led to a significant increase of the initial contact angle by 33% with water drop stability of over 200 s. In contrary, pure cellulose obtained no visible water drop and for surfaces with uncoupled hydrophobins no stable contact angle, with a soaking time dropping to 55 s was achieved. As a result, the thorough study revealed that the new combinatorial approach of surface functionalization and protein coupling led to the successful increase of hydrophobicity. [ABSTRACT FROM AUTHOR]

The development of inhibitors of anti-apoptotic proteins, such as Mcl-1, is currently a very active area in the field of cancer research. One of the very first reported inhibitors of Mcl-1 was the MIM1 molecule, but we have recently demonstrated that the structure of this compound had to be revised from 2 to the derivative 1 (FJ-809). In this paper we first develop a strategy to unambiguously prepare molecules such as 1 with a thiazol-3(2H)-yl)imino core, instead of the [2(3H)-thiazolylidene]hydrazine previously found in MIM1 (2). Next a series of biological studies have been performed on 1, using IGROV1-R10 ovarian cancer cells as models, and they have been complemented by fluorescence polarisation assays. These studies demonstrated that the new compound FJ-809 (1) was devoid of any significant activity on Mcl-1, in contrast to 2. Then molecular modelling and molecular dynamics studies have been performed in order to elucidate the differences between FJ-809 and MIM1 in their interaction with the Mcl-1 protein. [ABSTRACT FROM AUTHOR]

2-(Bis(pyridin-2-ylmethyl)amino) acetic acid (PIC) and ethylenediaminetetraacetic acid (EDTA) vehicle-based acetamidobenzoxazolone probes have been evaluated for the assessment of a 18 kDa translocator protein (TSPO). Here, PIC and EDTA work as a vehicle for possible binding of requisite metal and acetamidobenzoxazolone pharmacophore (MBP) has been used as a specific binding probe for TSPO. In silico interaction analysis was carried out to assess MBP's binding efficacy towards the TSPO. TSPO is a protein that is known to be overexpressed during inflammatory conditions, therefore, during in vivo experiments, an LPS-induced lung inflammation mouse model was developed for the administration of 99mTc-PIC-MBP and 99mTc-EDTA-MBP to understand absorption and distribution in several peripheral organs over time through SPECT imaging. In addition, photophysical analysis with serum protein, i.e., bovine serum albumin (BSA) was also performed using different spectroscopic techniques to understand the in vivo transportation/excretion of these two probes PIC-MPB and EDTA-MPB to better understand the nature of these probes as specific diagnostic agents. [ABSTRACT FROM AUTHOR]

A water-soluble Morita–Baylis–Hillman adduct (MBHA) derivative (3) was previously shown to self-assemble in a water environment into functional nanoreactors capable of performing multiple attacks and functionalization of N-acetylhexahistidine. In order to challenge this intriguing reactivity in a model protein more complex than N-acetylhexahistidine, the single-chain Fv antibody CRB0137 was characterized from the point of view of its structure and made to react with 3 in kinetics experiments. The results of these studies suggested that MBHA derivative 3 reacted typically with the amino acid residues of the CRB0137 hexahistidine tag leading to the formation of multi-PEGylated species. Overall, they demonstrate the viability of a new methodology for the site-specific PEGylation of engineered proteins bearing poly-histidine tags. [ABSTRACT FROM AUTHOR]

Attaching proteins to surfaces while maintaining bioactivity is a promising avenue for developing new functional materials. This work describes a method to rapidly apply bioactive coatings by conjugating protein into an adhesive network using an ortho-phthaldialdehyde (oPA)-based linker. The polymer matrix was generated using a copper-catalyzed azide–alkyne cycloaddition (CuAAC) polymerization on a commercial, antifouling copper-based paint that had not been previously examined as a catalytic material. After undergoing bioconjugation with the oPA linker, protein was retained at a higher rate on the surface when compared either with the control, which lacked a linker, or with a commercially-available maleimide linker. The ability to apply in situ, polymerize, and adhere biomacromolecules to surfaces while retaining their efficacy enables the creation of novel functional materials with properties usually reserved for the biological domains. [ABSTRACT FROM AUTHOR]

Cancer cells often overexpress and/or express de novo glycoproteins modified with short-chain sialylated O-glycans, sialyl-Tn (STn), sialyl-3-T (S3T) and sialyl-6-T (S6T) antigens, that hold potential for carbohydrate-based vaccines. However, the generation of glycopeptide libraries composed by structurally defined standards remains a critical step for carbohydrate metrology and vaccine development. A simple and fast multi-enzymatic single-pot method was applied for generating a wide array of STn, S3T and S6T glycopeptides. A 20-mer tandem repeat peptide from the cancer-associated glycoprotein MUC16 was used as a scaffold towards this end. Different glycosyltransferases and nucleotide sugars were combined in a stepwise manner to generate the glycopeptide libraries. TiO2 enrichment was further used to isolate sialoglycopeptides, and the glycopeptide libraries were characterized by nanoLC-MS. Multiple glycopeptides were conjugated with protein immunogens, bovine serum albumin (BSA) and keyhole limpet hemocyanin (KLH), foreseeing multivalent glycoepitopes that may pave the way for immunotherapy. We have synthesized MUC16-Tn antigens containing up to 5 glycosites and mapped the main occupied glycosites. We have also successfully synthesized MUC16-STn, S3T and S6T glycopeptides and hybrid MUC16-Tn/STn, MUC16-Tn/S3T, MUC16-T/S6T and MUC16-Tn/T/S6T glycoproteoforms. As proof-of-concept, we have coupled MUC16-Tn/STn glycopeptides to immunogenic proteins. This sets the molecular background for the future development of multivalent glycan-based vaccines exploiting MUC16 glycoepitopes. [ABSTRACT FROM AUTHOR]

The present study documents the first investigation into the relationship between the binding and cleavage activity of nickel complexes towards DNA and proteins. Here, three different NiII complexes of the general type [Ni(nal)2diimine] (1a and 1b) and [Ni(8-Hq)2(bpy)] 1c (nal = nalidixic acid, diimine = 2,2′-bipyridine (bpy) or 1,10-phenanthroline (phen), and 8-Hq = 8-hydroxyquinolone) have been isolated. The structural X-ray analysis clearly showed that all complexes possess cis octahedral geometry around the Ni atoms. The interaction of the complexes with proteins (BSA/HSA) and calf thymus (CT)-DNA was followed via a series of spectroscopic measurements. The observed results for the proteins revealed that the complexes quench the intrinsic fluorescence in static quenching mode with an excellent binding affinity towards both BSA and HSA. The DNA binding studies showed that the complexes readily bind with DNA via intercalative and minor groove modes with excellent binding affinities (1b > 1c > 1a). To understand the binding process of the complexes towards proteins and DNA, the thermodynamic Gibbs free energy (ΔG°), enthalpy (ΔH°) and entropy (ΔS°) parameters were also calculated and the obtained results indicated that the process is spontaneous and electrostatic. Moreover, the variation in the abilities of the complexes to cleave proteins and DNA have been explored via electrophoretic mobility spectrometry studies and the results revealed that all of the complexes exhibit excellent cleavage properties. Docking analysis with the crystal structures of BSA (4F5S), HSA (1AO6) and CT DNA (1BNA) was employed to study the ability of the complexes 1a–1c to bind to these target macromolecules. Finally, the in vitro anticancer activity of all three complexes was evaluated using the MTT assay against human lung (A-549) and breast (MCF-7) tumor cells for 24 h incubation times. [ABSTRACT FROM AUTHOR]

The phenanthroline appended glycoconjugate (L) and its Fe(II)-complex were synthesized and characterized using analytical and spectral methods. The complexation of Fe2+ with L has been shown using absorption and fluorescence spectral studies. 1H NMR titration of L with Fe2+ supports that the phenanthroline moiety acts as the metal binding core. The interaction and binding of the Fe-complex with calf thymus DNA (ct-DNA) were studied using spectral techniques, such as UV-Vis absorption, circular dichroism (CD) and DNA melting temperatures. The corresponding data supported the minor groove binding of ct-DNA by the Fe-complex along with electrostatic interactions. The gel electrophoresis studies carried out using pBR322 plasmid showed a tight binding of the iron complex with the plasmid and this resulted in the condensation of the pBR322 plasmid as revealed by the blob-like structures observed in the atomic force microscopy data. The binding of the Fe-complex by WGA was demonstrated by absorption, fluorescence and CD spectra, and the microstructures were observed via scanning electron microscopy (SEM). Star-like nanostructures observed via SEM support that the octahedral iron complex connects the protein molecules in three dimensions through their carbohydrate terminal moieties. Thus, a new Fe-complex possessing a biocompatible glucosyl moiety interacts and binds to biomolecules, such as DNA and protein, and the resulting species are of importance in biological applications. [ABSTRACT FROM AUTHOR]

The development of a robust and efficient stationary phase for chromatographic biopharmaceutical purification is of prime importance but remains challenging. Herein, we have developed a series of protein A-mesoporous silica composites for the first time by covalently coupling protein A with the tagged carbonyl imidazole moieties in the column, which constitutes a facile and efficient route for the preparation of protein A immunoaffinity materials. The resultant composites are employed as the stationary phase for chromatographic purification of immunoglobulin G (IgG). The effect of silica's pore size and coupled protein A on the antibody purification is systematically investigated. When the pore size of silica increased from 100 to 1000 Å, the amount of coupled protein A decreased, and the surface coverage on the silica significantly improved, accompanied by an increase in the amount of purified rabbit IgG. With an increasing coupled protein A, the surface coverage increased at first and decreased subsequently, which shows a similar trend to the amount of purified IgG and specific activity. When practically implemented for purifying several immunoglobulins that are central for commercial ELISA Kits, the protein A-mesoporous silica composite exhibited superior performance compared to the GE-Mabselcetxtra rProtein A column, particularly in the purification of immunoglobulin M (IgM), which cannot be realized by the GE-Mabselcetxtra rProtein A column. This study sheds new light on the rational development of protein-affinity chromatography for biopharmaceutical purification. [ABSTRACT FROM AUTHOR]

This article reports a computational kinetic and thermodynamic study of the chemical repair of radical-damaged tryptophan and tyrosine residues by the superoxide radical anion (O2˙−)–hydroperoxyl radical (HO2˙) pair, via single electron transfer (SET) and formal hydrogen transfer (FHAT) mechanisms. It was demonstrated that O2˙− can repair oxidized tyrosyl and tryptophanyl damaged residues, mainly by electron transfer, restoring them to their pristine structure. Acid–base equilibria were considered, and the influence of the pH on the main reaction mechanism was explored. The results presented here are expected to contribute to the better understanding of the complex and dual behaviour of the HO2˙–O2˙− in the context of oxidative stress. [ABSTRACT FROM AUTHOR]

The interaction of two bis-chelated VIVO2+ species, formed by pipemidic (Hpip) and 8-hydroxyquinoline-5-sulphonic acids (H2hqs), with two small proteins, ubiquitin (Ub) and lysozyme (Lyz), was studied by EPR, ESI-MS, docking and DFT methods. The two complexes differ in electric charge (at neutral pH it is +2 and −2 for the species of Hpip and H2hqs, respectively), coordination geometry (cis-[VO(Hpip)2(H2O)]2+ is in equilibrium with the square pyramidal [VO(Hpip)2]2+, while cis-[VO(hqs)2(H2O)]2− is the only species in solution), and size (pipemidic acid is more sterically crowded than 8-hydroxyquinoline-5-sulphonic acid). The ESI-MS spectra showed that the number of cis-VO(hqs)22− moieties which interact with Ub is twice that of cis-VO(Hpip)22+ (adducts with formula n[VOL2]–Ub, where n = 1–4 for H2hqs and n = 1–2 for Hpip, were detected). The data can be rationalized in terms of the lower steric requirements of hqs2− and its negative charge, which favour secondary interactions with the surface groups of the protein. The EPR spectra revealed the coordination of Asp/Glu-COO or His-N donors, while docking calculations allowed us to identify the Ub residues involved in the VO(Hpip)2 (Asp39 and His68) and VO(hqs)2 binding (Glu18, Asp39, Asp58 and His68). The steric hindrance of Hpip is so important that the interaction of cis-[VO(Hpip)2(H2O)]2+ with lysozyme is completely prevented, while with cis-[VO(hqs)2(H2O)]2− the adducts n[VO(hqs)2]–Lyz (n = 1–2) were detected. Finally, the general effect of secondary interactions such as hydrogen bonds and van der Waals contacts, steric hindrance and electric charge on the V binding and stability of the adducts formed is also discussed, suggesting that these factors should be taken into account when designing new pharmacologically active compounds. [ABSTRACT FROM AUTHOR]

The early protein HPV E6 of human papillomavirus is the major oncoprotein in high-risk subtypes. Due to its critical role in malignant tumorigenesis, it is a widely recognized biomarker for the early diagnosis of HPV-related cancers. The lack of effective and commercially available monoclonal antibodies (mAbs) against HPV16 E6 makes the sensitive detection of HPV16 E6 a great challenge. In the present study, DNA-protected silver nanoclusters (AgNCs–dsDNA) were used as a sensitive fluorescent probe for the detection of HPV E6. Both the emission enhancement and the blue shift induced by HPV E6 provide a new approach for the detection of this protein in vitro. This method exhibits a high sensitivity (LOD of 0.886 nM), good selectivity and strong anti-interference to several common proteins, which can also be applied for the detection of HPV 16 E6 in bovine serum. Therefore, it shows potential utility in the clinical diagnosis of related cancers. Particularly, the intrinsic mechanism of the highly sensitive response of AgNCs–dsDNA to HPV E6 was explored in detail by choosing several representative peptides from E6, and it was revealed that in addition to the electrostatic interaction between them, the involved cysteine was essential for the specific recognition of this protein; therefore, the response of AgNCs–dsDNA to the protein was due to the synergistic effect of different factors, and the cysteine residue was the dominant factor. The oppositely charged surfaces of E6 and AgNCs–dsDNA attract each other via electrostatic interactions, and then, E6 is anchored onto the surface of the nanocluster via the newly formed Ag–S bond; the present study not only enriches the biological application of metal nanoclusters but also shows significant potential for the early diagnosis of the HPV-induced cancers. [ABSTRACT FROM AUTHOR]

The interference of NAMI-A ([ImH][RuCl4(Im)(DMSO)], Im – imidazole, DMSO – dimethyl sulfoxide) with the metabolism of nitric oxide (NO) has been proposed as one of the possible pathways of the antimetastatic activity of this complex. With regard to this observation we present herein detailed spectrophotometric studies on interaction of the NAMI-A complex with NO. The reactivity of NAMI-A toward NO has been studied in aqueous solution under physiological-like conditions (pH = 7.4, [NaCl] = 0.1 M, T = 37 °C). The ability of NAMI-A as well as its hydrolytic products to bind NO has been confirmed spectrophotometrically and separation of reaction products was performed with application of the HPLC technique. The relatively slow NO binding requires opening up a coordination site in the parent NAMI-A complex via simultaneously occurring hydrolysis. The studies in the presence of albumin showed that NO can coordinate to NAMI-A–albumin adducts. The capability of nitrosyl derivatives (Ru2+–NO+) to undergo reduction of the NO+ moiety in the presence of ascorbic acid, glutathione and dithionite has been studied with application of the NO sensor. The obtained results showed that under selected conditions, nitrosyl complexes cannot liberate nitric oxide via one electron reduction using applied reductants. This is due to the relatively low reduction potential of the NO+ group bound to Ru(ii) (−0.69 V), determined in electrochemical studies. [ABSTRACT FROM AUTHOR]

The present investigation attempts to separate the variation in time domain from steady-state fluorescence and to discuss quantitatively the state-switching of α-chymotrypsin (CHT). The activity of CHT is pH dependent (inactive at low pH, such as 2.2, but active at physiological pH, such as 8). ANS (1-anilinonaphthalene-8-sulfonate) has two states of fluorescence corresponding to different excitation and emission processes. Though a steady-state technique, Excitation–Emission Matrix fluorescence (EEM) can record all the excitation and emission signals for the ANS–CHT complex system. The trilinear decomposition of the constructed three-way data set (using EEM data of different samples) can provide excitation and emission spectra indicating specific excitation and emission processes, respectively, and a quantitative description for the time domain processes. Besides a detailed description of the excitation–emission processes of ANS, the quantitative investigation of state-switching by CHT is also possible because the fluorescence, due to the S1,ct state of ANS, is sensitive to the solvation environment, which is one of the indicators of CHT activity. Finally, the switching output curve of the ANS–CHT system over a wide pH range is obtained. This study proposes a convenient and economical protocol for investigating state-switching in proteins. [ABSTRACT FROM AUTHOR]

LuxS is an important protein involved in the synthesis of Autoinducer 2, the signaling molecule in the quorum sensing system for the communication of Gram-positive and Gram-negative bacteria. Therefore, the LuxS protein is a potential target for inhibiting the production of biological phenomena in pathogenic bacteria that could control several diseases such as periodontal disease and caries among others. A comparative molecular similarity indices analysis (CoMSIA) study was conducted with 20 analogues of ribosylhomocysteine (RHC) and KRI, which are native ligands of the LuxS protein. Due to the change of the oxygen atom in position 7 in the proposed inhibitor INH-KRI 02 for the sulfur atom and the stereochemistry of the carbon in position 4, there was a possible variation of the hydrophobic, hydrogen bond donor and acceptor fields, which were observed as predominant over the steric and electrostatic fields in the obtained dockings. The presence of a sulfur atom can be fundamental in the inhibition of the LuxS protein. This increase seems to improve the lipophilicity due to changes of atoms in several positions, indicating an improvement in the predicted activity of the ligands compared with other previously described ligands. [ABSTRACT FROM AUTHOR]

Novel scaffolds of stilbene were identified as inhibitors of Mycobacterium tuberculosis by targeting the nucleoid-associated protein, HU, using molecular docking. Based on the proposed combinatorial libraries I to VI, structures I and III had significantly greater docking binding energy that was comparable to that of the reference ligand, protein HU, from Mycobacterium tuberculosis. Using these docking results, 18 compounds were synthesized, characterized and evaluated for in vitro antitubercular (anti-TB) efficacy in the Mycobacterium tuberculosis strain, H37Rv. The in vitro screening results indicated a significant positive correlation between the docking binding efficacy (r2 > 0.5) and clogp. Compounds 3f, 3d and 4f were ranked as top scoring ligands that interacted with amino acids ARG 53, ARG 55, PRO 81, PHE 79, and LYS 13, where the –NO2 or –Cl substitution at the para position of the 3-phenyl ring was essential for interacting of the HU protein. The hydrogen bonding with ARG 55 and LYS 13 of these compounds was similar to that with the reference ligand that inhibits the HUMtb protein. Compounds 3d, 3f, and 4f were evaluated as active leads, with MIC90 values of 21.3, 23.2 and 44.1 μM, respectively. The above mentioned compounds were also evaluated for antibacterial and antifungal efficacy in a panel of selected bacteria and fungi. Compound 3d had efficacy (MIC90: 6.82 μM) in S. aureus and E. coli. Compound 3f was also efficacious in E. coli and A. Niger, with an MIC90 value of 7.42 μM for both microorganisms. The fluoro-phenyl derivatives, 3i and 4i, were efficacious in C. albicans (MIC90 values of 8.2 and 7.8 μM, respectively) and A. niger (MIC90 values of 4.1 and 3.1 μM, respectively). Our results suggest that substitutions at the para position of 3-phenyl acryl derivatives with –NO2 and –Cl significantly affected the binding interactions with the HUMtb protein in the docking studies. Furthermore these compounds had antitubercular and antimicrobial efficacy. The substituted phenyl acrylic acid and hydrazides could be inhibitors of the HUMtb protein of Mycobacterium tuberculosis. [ABSTRACT FROM AUTHOR]

In this work, we prepared poly- L -lysine (PLL) functionalized magnetic graphene through a simple covalent bonding process. The composite was further conjugated with aspartic acid (Asp) and chelated copper ions to obtain a metal affinity PLL-functionalized magnetic graphene composite (MGPLA-Cu). Various characterizations via FT-IR, XRD, TGA, VSM and SEM/TEM confirm its physicochemical properties. Owing to the strong metal affinity forces between metal affinity groups and the residual histidine in proteins, the MGPLA-Cu composite exhibits highly selective adsorption performance toward histidine-rich proteins, i.e., hemoglobin (Hb) in this case. A high adsorption efficiency of ca. 100% was achieved for 200 mg L−1 Hb in a phosphate buffer at pH 8. The equilibrium adsorption isotherm of Hb on the MGPLA-Cu composite well fitted to the Langmuir theoretical model (R2 = 0.9969), along with the maximum adsorption capacity (qmax) at 334 mg g−1. The adsorption kinetics was favorably described by the pseudo-second-order kinetic model. The retained Hb could be effectively recovered with a 0.2 mol L−1 carbonate buffer containing 0.05 mol L−1 imidazole at pH 10, giving rise to a recovery of ca. 97%. The MGPLA-Cu composite showed favorable reusability, and a high adsorption efficiency (>80%) was maintained after five adsorption–desorption operation cycles. The practical application demonstrates that the MGPLA-Cu composite can isolate Hb from human whole blood with high selectivity and high purity. [ABSTRACT FROM AUTHOR]

A facile solution based chemical route has been developed for the synthesis of cuprous oxide (Cu2O) octahedrons employing polyvinylpyrrolidone (PVP ∼ 10k) at a relatively low temperature (50 °C) in aqueous medium and their response towards electrochemical non-enzymatic glucose sensing has been precisely investigated. The amperometric analysis reveals two calibration ranges (0.1 μM–1 mM and 1–7 mM) for the modified electrodes, with an excellent glucose specific selectivity over other interfering materials like sucrose, fructose, ascorbic acid (AA) and dopamine (DA). Careful analysis of the amperometric outcomes unveils a low limit of detection (LOD) of 0.96 μM (S/N = 3) along with exceptionally good stability and repeatability. Furthermore, the octahedral Cu2O modified electrodes exhibit a fast response time (∼1.5 s) with acceptable sensitivity and are found to be exceedingly reliable for the real time analysis of human serum samples (relative error <3.2%) compared to commercial glucose biosensors. Detailed survey of the adsorption of four most common blood proteins onto the negatively charged surface of Cu2O octahedrons using steady state fluorescence, dynamic light scattering (DLS), zeta potential (ζ) and circular dichroism (CD) in aqueous dispersions delineates the electrostatic interaction driven low protein adsorption that strongly indicates their further potential applicability in medical devices for targeted monitoring of glucose. [ABSTRACT FROM AUTHOR]

Observation of apparently never-ending lag-phase in the fibrillation of serum albumins (SAs) with low concentration of methotrexate (MTX) appears very promising and quite unique for clinical implications toward prevention of aggregation-related disorders. In the present work, we showcase that thermally induced bovine serum albumin (BSA) and human serum albumin (HSA) fibrillation is significantly inhibited by folic acid (FA), and completely by MTX. Surflex-docking, molecular dynamics (MD) simulation and aggregation-propensity studies provide a molecular level scenario that justifies the longer lag-phase in kinetics or high suppression of fibrillation by drugs. [ABSTRACT FROM AUTHOR]

Conformational preferences of the 2-methylproline (2-MePro) residue and its role in stabilizing β-turn and polyproline II (PII) structures of peptides have been studied using density functional methods in the gas phase and in water. The population of the C7 H-bonded structures of Ac-2-MePro-NHMe is calculated to be dominant in the gas phase, whereas they become significantly depopulated and the populations of polyproline and α-helical structures increase in water. Due to the increased stability of the up-puckered PII structure, the populations of its PII and PI structures are more increased by 10.9% and decreased by 12.2% than Ac-Pro-NHMe in water, respectively. There is a large decrease in the cis population by 20.6% for the prolyl peptide bond by replacing Pro with 2-MePro in water, which is consistent with 13C NMR experiments. For Ac-Ala-2-MePro-NHMe, the conformer with a βI-turn is found to be the most preferred conformer with the population of 25.2% in water, whereas the open conformers are dominantly populated for Ac-Ala-Pro-NHMe. This is consistent with experimental results that the Ala-Pro sequence of the antigen mimotope associated with autoimmune recurrent thrombosis has been known to adopt a stable βI-turn structure with the replacement of Pro by 2-MePro in water. With the replacement of a single Pro by 2-MePro in the middle of the sequences of the polyproline model peptide Ac-(Pro)5-NMe2 and the single-strand model peptide of collagen Ac-(Hyp-Gly-Pro)2-NMe2, the relative stabilities of the PII structures are enhanced by 8.11 and 3.91 kcal mol−1, respectively, although there are only small changes in backbone torsion angles of both PII and PI structures. It can be deduced that the single strands of (Hyp-Gly-2-MePro)n with the stable PII structure might provide more stability to their triple helix. [ABSTRACT FROM AUTHOR]

We perform density functional studies to comprehend the structure and energetics of the interaction of the drug pyrazinamide (PZA) with graphene-based nanomaterials using a noncovalent functionalization approach, followed by molecular docking on the PZA–nanosheet system with the pncA protein. The structural deformation within the nanosheet induced by adsorbed PZA, adsorption energies and global reactivity descriptors are compared for the studied systems at all probable adsorption sites. Significant crumpling of the nanosheets is observed upon adsorption of PZA, with the effect being more pronounced for defect modified, BN and Stone–Wales (SW) defect nanosheets. The inclusion of dispersion corrected DFT (DFT-D) calculations takes into account the weak noncovalent van der Waals π–π stacking and the variation of adsorption energy, energy gap and dipole moment are compared with the results of DFT–GGA. Docking studies help in predicting the plausible binding mechanism between nanosheet–PZA systems and pncA protein and suggests that PZA loaded onto the nanomaterials facilitates the target binding of the drug within the protein. Interestingly, presence of nanosheets does not induce any major structural deformation in the protein, with the interaction between ligand and receptor being mainly hydrophobic in nature, and the doped nanosheets are found to be better docked compared to perfect sheets. [ABSTRACT FROM AUTHOR]

Literature data on partitioning of compounds from the gas phase to a number of amides and from water to the amides has been collected and analyzed through the Abraham solvation equations. The resulting equations are statistically good enough to be used for the prediction of further partition coefficients, and allow deductions to be made about the chemical properties of the amides, as solvents. For example, tertiary amides have no hydrogen bond property at all, secondary amides are rather weak hydrogen bond acids, and primary amides are stronger hydrogen bond acids than are alcohols as solvents. Equations for partitioning from the gas phase to amide solvents can also be used to test if the amides are possible models for a number of biological phases and biological processes. It is shown that no organic solvent is a suitable model for phases such as blood, brain, muscle, liver, heart or kidney, but that a number of rather non-polar solvents are models for fat. N-Methylformamide is shown to be the best (and excellent) model for eye irritation and nasal pungency in humans, suggesting that the receptor site in these processes is protein-like. [ABSTRACT FROM AUTHOR]

During the last forty years, enzyme-base biosensors have had great success in the detection and quantification of various biologically-relevant molecules. However, native enzymes can sometimes be costly, delicate to manipulate or simply absent for a particular analyte. Hence, artificial or synthetic enzymes could be a useful alternative to natural proteins for the conception of new biosensors, since they can be, a priori, designed in their entirety, as well as more robust, available, chemically malleable and cheap, in comparison with their natural analogues. In this Perspective, we will provide a snapshot of this emerging research field. [ABSTRACT FROM AUTHOR]

The role of CuII-complexation of amyloidogenic peptides on the formation and structure of aggregates were analyzed in order to obtain a general insight into modulation of peptide aggregation by metal ions. The results mimicked various facets of biological relevant peptides/protein-aggregation. Important mechanistic features are the ability of CuII to associate the peptides by bridging coordination, the structural changes induced by CuII binding and their effect on peptide–peptide interactions. [ABSTRACT FROM AUTHOR]

A combination of two model approaches was used to explore the nature of silicone–protein interactions. Phage display technology was used to present a combinatorial library of peptides, in this case the phage library PhD.-12, to a series of model silicone surfaces. Solid, molecular cage silsesquioxanes were used as the models for silicone surfaces. The silsesquioxanes were octamethyloctasilsesquioxane (methyl8-T8), octaphenyloctasilsesquioxane (phenyl8-T8), octahydridooctasilsesquioxane (H8-T8) and dodecatrifluoropropyldodecasilsesquioxane (trifluoropropyl12-T12). The first two silsesquioxanes bear simple aliphatic (Me) and aromatic (Ph) pendant groups, and are simple silicone analogues. The second two silsesquioxanes have functionalised pendant groups, H and CF3CH2CH2. The panning results, using a wild-type phage as a control, show that the phage library binds to the simple aliphatic and aromatic silsesquioxanes strongly but non-specifically, and largely through the protein coat on the phage. The functionalised silsesquioxanes (H and CF3CH2CH2) are bound specifically by the phages. A statistical analysis of the DNA sequences of the strongly binding phages was carried out. The peptides that bind to H8-T8 are strongly enriched in proline content at positions 7 and 8, with enhanced histidine at positions 5 and 9, and enhanced threonine at position 11. The proline residues presumably induce a favourable conformation in the peptide for binding to the silsesquioxane surface. The enhanced histidine content is significant. It has been known for many years that imidazole has a particular affinity for electrophilic silanes. The amino acid distribution for trifluoropropyl12-T12 binding peptides is markedly different from that of H8-T8 silsesquioxane. Proline is again enhanced, but in positions 4, 11 and 12, and there are also very high concentrations of serine in positions 1, 9 and 11, and threonine in positions 1, 2 and 12. The highly polar nature of the CF3 group is likely to engage in hydrogen bonding with the OH groups of the serine and threonine side chains, accounting for the tight binding to trifluoropropyl12-T12 silsesquioxane. [ABSTRACT FROM AUTHOR]