Traceless synthesis of protein thioesters using enzyme-mediated hydrazinolysis and subsequent self-editing of cysteinyl prolyl sequence

A traceless thioester-producing protocol featuring carboxypeptidase Y-mediated hydrazinolysis of cysteinyl prolyl leucine-tagged peptides has been developed. The hydrazinolysis followed by thioesterification affords cysteinyl prolyl thioesters. Self-editing of the tag and subsequent trans-thioesterification yields peptide thioesters. The developed protocol was successfully applied to conversion of recombinant proteins to thioesters

Synthesis of lactam-bridged cyclic peptides using sequential olefin metathesis and diimide reduction reactions

A new approach has been developed for the synthesis of lactam-bridged cyclic peptides. Following the introduction of N-allyl glutamine and α-allylglycine into the peptide backbone, the side chains of these residues were subjected to a cyclization reaction by ring-closing metathesis (RCM). Reduction of the resulting peptide bearing olefin moiety was achieved using diimide, which was generated in situ from o-nitrobenzenesulfonyl hydrazine and piperidine, gave the corresponding saturated cyclic peptides

Synthesis of lactam-bridged cyclic peptides using sequential olefin metathesis and diimide reduction reactions

A new approach has been developed for the synthesis of lactam-bridged cyclic peptides. Following the introduction of N-allyl glutamine and α-allylglycine into the peptide backbone, the side chains of these residues were subjected to a cyclization reaction by ring-closing metathesis (RCM). Reduction of the resulting peptide bearing olefin moiety was achieved using diimide, which was generated in situ from o-nitrobenzenesulfonyl hydrazine and piperidine, gave the corresponding saturated cyclic peptides

A photoinduced growth system of peptide nanofibres addressed by DNA hybridization

Spatiotemporal control of peptide nanofibre growth was achieved by photocleavage of a DNA-conjugated β-sheet forming peptide that is linked through a photoresponsive amino acid residue. Peptide nanofibres were selectively formed by photocleaving the conjugate on complementary DNA-immobilised glass substrate

Liquid-Phase Synthesis of Bridged Peptides Using Olefin Metathesis of a Protected Peptide with a Long Aliphatic Chain Anchor

Bridged peptides including stapled peptides are attractive tools for regulating protein-protein interactions (PPIs). An effective synthetic methodology in a heterogeneous system for the preparation of these peptides using olefin metathesis and hydrogenation of protected peptides with a long aliphatic chain anchor is reported

Development of an intein-inspired amide cleavage chemical device

A photo-responsive amide cleavage device was developed based on the asparagine imidation-mediated cleavage of peptide bonds during intein-mediated protein splicing. The chemical environment of the protein splicing process was mimicked by the incorporation of geminal dimethyl groups and a secondary amine unit in asparagine scaffold. Furthermore, the resulting photo-responsive device could induce the photo-triggered cleavage of an amide bond by the protection of the secondary amine unit with an o-nitrobenzyloxycarbonyl group

Design and synthesis of a hydrogen peroxide-responsive amino acid that induces peptide bond cleavage after exposure to hydrogen peroxide

Oxidative stress-responsive compounds are attracting significant attention in the field of medicinal chemistry and chemical biology. Here, we disclose the development of a hydrogen peroxide (H2O2)-responsive amino acid that induces peptide bond cleavage in the presence of H2O2 that closely relates to the oxidative stress. The H2O2-responsive amino acid possessing a boronate or boronic acid moiety was incorporated into a peptide using Fmoc-based solid-phase peptide synthesis or that with minor modification, respectively, and the peptide bond cleavage of the obtained peptide was successfully triggered by the addition of H2O2

Development of a traceable linker containing a thiol-responsive amino acid for the enrichment and selective labelling of target proteins

A traceable linker that is potentially applicable to identification of a target protein of bioactive compounds was developed. It enabled not only thiol-induced cleavage of the linker for enrichment of the target protein but also selective labelling to pick out the target from contaminated non-target proteins for facile identification