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In the present work, combining polymerization‐induced self‐assembly (PISA) with self‐assembling peptides (SAPs) peptide−polymer hybrid nanostructures are prepared, harnessing the advantages of PISA and the self‐assembling driving force of SAPs. A tripeptide methacrylamide denoted as MAm‐GFF, where MAm, G, and F stand for methacrylamide, glycine, and phenylalanine, is copolymerized with glycerol monomethacrylate (GMA) by reversible addition−fragmentation chain transfer polymerization (RAFT) in dimethylformamide to produce a P(GMA62‐stat‐(MAm‐GFF)7) macromolecular chain transfer agent (macro‐CTA). This peptide‐containing macro‐CTA is then successfully chain‐extended with poly(2‐hydroxypropyl methacrylate) (PHPMA) by aqueous dispersion PISA, forming P(GMA62‐stat‐(MAm‐GFF)7)‐b‐PHPMA27 self‐assembled objects. The impacts of temperature and monomer conversion on the morphologies formed during the PISA process are investigated by analyzing samples withdrawn at different time during the polymerization of HPMA using transmission electron microscopy (TEM) and dynamic light scattering (DLS) at different temperatures (5–70 °C). [ABSTRACT FROM AUTHOR]

N‐terminal derivatization of proteins with permanently positive charged reagent constitutes a viable mass spectrometry bottom‐up strategy for systematic confident identification of protein N‐termini. Although shotgun nanoLC‐ESI‐MS/MS approaches are commonly applied in that context by dissociating multiply charged molecular ions upon low energy collision‐induced dissociations (CID), we were keen to investigate an alternative sequencing method reckoning on more comprehensive high energy charge remote fragmentations (CRF) available with a MALDI‐Tof/Tof instrument. Hence, two tunable activation methods, i. e. metastable laser‐induced dissociations (LID) and high energy CID, were applied to several synthetic N‐terminal tris(trimethoxyphenyl)phosphonium (TMPP) acetyl peptides and their MS/MS behaviors were compared with low energy CID MS/MS data (LC‐ESI‐QqTof equipment). The amino acid composition was found to play a significant role in the peptide backbone dissociation pathways of these fixed singly charged ions. Proline, arginine, aspartic acid, glutamic acid, but also surprisingly aliphatic residues were impacting the expected sequence fragmentation pattern. [ABSTRACT FROM AUTHOR]

Synthesis of long peptides is generally considered as a challenge to peptide chemists, in addition to producing significant amounts of toxic waste, such as DMF. Here we show that using solvent‐less methods, such as ball milling, enabled the production of the hexapeptide Boc‐(Ala‐Phe‐Gly)2‐OBn at the gram scale with high overall yield (77 %, 5 linear steps). This is the longest peptide chain synthesized in a ball mill to date, in which the amino acid sequence is precisely controlled. This study complements the current fundamental knowledge required to synthesize longer and more difficult peptide chains (or small proteins) by using peptide fragment couplings in a ball mill. [ABSTRACT FROM AUTHOR]

A simple and efficient way to synthesize peptide‐containing silicone materials is described. Silicone oils containing a chosen ratio of bioactive peptide sequences were prepared by acid‐catalyzed copolymerization of dichlorodimethylsilane, hybrid dichloromethyl peptidosilane, and Si(vinyl)‐ or SiH‐functionalized monomers. Functionalized silicone oils were first obtained and then, after hydrosilylation cross‐linking, bioactive polydimethylsiloxane (PDMS)‐based materials were straightforwardly obtained. The introduction of an antibacterial peptide yielded PDMS materials showing activity against Staphylococcus aureus. PDMS containing RGD ligands showed improved cell‐adhesion properties. This generic method was fully compatible with the stability of peptides and thus opened the way to the synthesis of a wide range of biologically active silicones. [ABSTRACT FROM AUTHOR]

The sol‐gel process can be used for hydrogel cross‐linking, thus opening an attractive route for the design of biocompatible hydrogels under soft conditions. The sol‐gel process can be catalysed at basic or acidic pH values, under neutral conditions with the addition of a nucleophile. Therefore, working around pH 7 unlocks the possibility of direct cell embedment and the preparation of bioinks. We aimed to propose a generic method for sol‐gel 3D bioprinting, and first screened different nucleophilic catalysts using bis‐silylated polyethylene glycol (PEG) as a model hydrogel. A synergistic effect of glycine and NaF, used in low concentrations to avoid any toxicity, was observed. Biocompatibility of the approach was demonstrated by embedding primary mouse mesenchymal stem cells. The measure of viscosity as a function of time showed the impact of reaction parameters, such as temperature, complexity of the medium, pH and cell addition, on the kinetics of the sol‐gel process, and allowed prediction of the gelation time. [ABSTRACT FROM AUTHOR]

We took advantage of the powerful adenine SERS (Surface Enhanced Raman Spectroscopy) probe to design peptide–adenine conjugates as candidates for use as serine protease substrates. Whereas the direct introduction of the peptide sequence on the adenine exocyclic N6 amine gave an imidazopurinone derivative, the introduction of an aminoethyl linker between the adenine group and the peptide chain led to the expected candidate probes. These potential substrates were then evaluated for monitoring the hydrolytic activity of trypsin, used as a model protease, by HPLC and by SERS. We demonstrated that the Boc–VPR–adenine conjugate is a substrate of trypsin and constitutes a good starting point to design optimized substrates to monitor protease activity by SERS. We report an efficient way to synthesize challenging peptide–adenine conjugates as alternative to the aminomethylcoumarine (AMC)‐serine protease substrates. [ABSTRACT FROM AUTHOR]

Abstract: Advanced drug delivery systems (DDS) are easily designed following a photoiterative strategy. Multifunctional polymers are obtained by coupling building blocks of interest to an alkynated poly(ε‐caprolactone) (PCL) platform via an efficient thiol–yne photoaddition. Fine‐tuning over the design is achieved, as illustrated with targeting and enzyme‐responsive DDS. [ABSTRACT FROM AUTHOR]

Background and Purpose: Using an in-house bioinformatics programme, we identified and synthesized a novel nonapeptide, H-Pro-Pro-Thr-Thr-Thr-Lys-Phe-Ala-Ala-OH. Here, we have studied its biological activity, in vitro and in vivo, and have identified its target in the brain.Experimental Approach: The affinity of the peptide was characterized using purified whole brain and striatal membranes from guinea pigs and rats . Its effect on behaviour in rats following intra-striatal injection of the peptide was investigated. A photoaffinity UV cross-linking approach combined with subsequent affinity purification of the ligand covalently bound to its receptor allowed identification of its target.Key Results: The peptide bound with high affinity to a single class of binding sites, specifically localized in the striatum and substantia nigra of brains from guinea pigs and rats. When injected within the striatum of rats, the peptide stimulated in vitro and in vivo dopamine release and induced dopamine-like motor effects. We purified the target of the peptide, a ~151 kDa protein that was identified by MS/MS as angiotensin converting enzyme (ACE I). Therefore, we decided to name the peptide acein.Conclusion and Implications: The synthetic nonapeptide acein interacted with high affinity with brain membrane-bound ACE. This interaction occurs at a different site from the active site involved in the well-known peptidase activity, without modifying the peptidase activity. Acein, in vitro and in vivo, significantly increased stimulated release of dopamine from the brain. These results suggest a more important role for brain ACE than initially suspected. [ABSTRACT FROM AUTHOR]

The O -N acyl transfer reaction has gained significant popularity in peptide and medicinal chemistry. This reaction has been successfully applied to the synthesis of difficult sequence-containing peptides, cyclic peptides, epimerization-free fragment coupling and more recently, to switchable peptide polymers. Herein, we describe a related strategy to facilitate the synthesis and purification of a hydrophobic stapled peptide. The staple consists of a serine linked through an amide bond formed from its carboxylic acid function and the side chain amino group of diaminopropionic acid and through an ester bond formed from its amino group and the side chain carboxylic acid function of aspartic acid. The α-amino group of serine was protonated during purification. Interestingly, when the peptide was placed at physiological pH, the free amino group initiated the O-N shift reducing the staple length by one atom, leading to a more hydrophobic stapled peptide. Copyright © 2016 European Peptide Society and John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

The conformational control of molecular scaffolds allows the display of functional groups in defined spatial arrangement. This is of considerable interest for developing fundamental and applied systems in both the fields of biology and material sciences. Peptides afford a large diversity of functional groups, and peptide synthetic routes are very attractive and accessible. However, most short peptides do not possess well-defined secondary structures. Herein, we developed a simple strategy for converting peptide sequences into structured g-lactam-containing oligomers while keeping the amino acids side chain diversity. We showed the propensity of these molecules to adopt ribbon-like secondary structures. The periodic distribution of the functional groups on both sides of the ribbon plane is encoded by the initial peptide sequence. [ABSTRACT FROM AUTHOR]

A series of arylpiperazinylbutyl derivatives of 4,5-dihydro-1,2,4-triazine-6( 1H)-ones was designed and synthesized according to the new solid-supported methodology. In this approach, triazinone scaffold was constructed from the Fmoc-protected glycine. The library representatives showed different levels of affinity for 5- HT7 and 5- HT1A receptors; compounds 13, 14 and 18- 20 were classified as dual 5- HT7/5- HT1A receptors ligands. The structure-affinity relationship analysis revealed that the receptor affinity and selectivity of the tested compounds depended on the kind of substituent in position 3 of triazinone fragment as well as substitution pattern of the phenylpiperazine moiety. [ABSTRACT FROM AUTHOR]

We describe a new class of silicone-containing peptide polymers obtained by a straightforward polymerization in water using tailored chlorodimethylsilyl peptide blocks as monomeric units. This general strategy is applicable to any type of peptide sequences, yielding linear or branched polymer chains composed of well-defined peptide sequences. [ABSTRACT FROM AUTHOR]

We have recently reported on a new class of silicone-peptide‵ biopolymers obtained by polymerization of di-functionalized chlorodimethylsilyl hybrid peptides. Herein, we describe a related strategy based on dichloromethylsilane-derived peptides, which yield novel polymers with a polysiloxane backbone, comparable with a silicone-bearing pendent peptide chains. Interestingly, polymerization is chemoselective toward amino acids side-chains and proceeds in a single step in very mild conditions (neutral pH, water, and room temperature). As potential application, a cationic sequence was polymerized and used for antibacterial coating. Copyright © 2015 European Peptide Society and John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

A mild, practical, and simple procedure for peptide-bond formation is reported. Instead of activation of the carboxylic acid functionality, the reaction involves an unprecedented use of activated α-aminoesters. The method provides a straightforward entry to dipeptides and was effective when a sensitive cysteine residue was used, as no epimerization was detected in this case. The applicability of this method to iterative peptide synthesis was illustrated by the synthesis of a model tetrapeptide in the challenging reverse N→C direction. [ABSTRACT FROM AUTHOR]

Six extended analogues of the recently described peptides (LDVL, ADVL) were designed and synthesized on a solid support, and then impregnated on TLC stationary phases. The impact of the impregnated peptide sequence modifications on the chromatographic retard, Δ Rf (difference in the migration of tested compound on control and impregnated plates), of 42 arylpiperazine 5-HT1A receptor ligands was studied. None of the new models tested made a better prediction of 5-HT1A affinity than that utilizing ADVL tetrapeptide. Further validation of the ADVL model on a set of 22 structurally differentiated 2-methoxy-phenylpiperazine derivatives confirmed its effectiveness in the affinity discrimination of a coherent group of 5-HT1A receptor ligands. Copyright © 2004 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

A series of arylpiperazinylbutyl derivatives of 4,5-dihydro-1,2,4-triazine-6(1H)-ones was designed and synthesized according to the new solid-supported methodology. In this approach, triazinone scaffold was constructed from the Fmoc-protected glycine. The library representatives showed different levels of affinity for 5-HT7 and 5-HT1A receptors; compounds 13, 14 and 18-20 were classified as dual 5-HT7 /5-HT1A receptors ligands. The structure-affinity relationship analysis revealed that the receptor affinity and selectivity of the tested compounds depended on the kind of substituent in position 3 of triazinone fragment as well as substitution pattern of the phenylpiperazine moiety., (© 2015 John Wiley & Sons A/S.)