title: Invention of stimulus-responsive peptide-bond-cleaving residue (Spr) and its application to chemical biology tools.
abstract: Elucidation of biological functions of peptides and proteins is essential for understanding peptide/protein-related biological events and developing drugs. Caged peptides and proteins that release a parent active peptide/protein by photo-irradiation have successfully been employed to elucidate the functions. Whereas the usual caged peptide/protein enables conversion of an inactive form to an active form (OFF-to-ON conversion) by photo-induced deprotection, photo-triggered main chain cleavage is reported to be applicable to ON-to-OFF conversion. These peptides and proteins are photo-responsive; however, if peptides and proteins could respond to other stimuli such as disease-related environment or enzymes, their range of application should be widened. To convert the photo-responsive peptide/protein into other stimulus-responsive peptide/protein, quite laborious de novo design and synthesis of the stimulus-responsive unit are required. In this context, we designed a stimulus-responsive peptide-bond-cleaving residue (Spr) in which the stimuli available for the main chain cleavage vary according to the choice of protecting groups on the residue. In this review, design and synthesis of Spr are introduced, and challenges to apply Spr to other fields to enable, for example, functional control, localization control, delivery of cargos, labeling of a protein of interest in living cells, and identification of target proteins of bioactive ligands are discussed. Copyright © 2017 European Peptide Society and John Wiley & Sons, Ltd.
authors.affiliation: Institute of Biomedical Sciences and Graduate School of Pharmaceutical Sciences, Tokushima University, 1-78-1 Shomachi, Tokushima, 770-8505, Japan.|PRESTO, Japan Science and Technology Agency (JST), 4-1-8 Honcho, Kawaguchi, Saitama, 332-0012, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Shigenaga
authors.affiliation: Institute of Biomedical Sciences and Graduate School of Pharmaceutical Sciences, Tokushima University, 1-78-1 Shomachi, Tokushima, 770-8505, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Yamamoto
authors.affiliation: Institute of Biomedical Sciences and Graduate School of Pharmaceutical Sciences, Tokushima University, 1-78-1 Shomachi, Tokushima, 770-8505, Japan.
authors.forename: Taiki
authors.initials: T
authors.lastname: Kohiki
authors.affiliation: Institute of Biomedical Sciences and Graduate School of Pharmaceutical Sciences, Tokushima University, 1-78-1 Shomachi, Tokushima, 770-8505, Japan.
authors.forename: Tsubasa
authors.initials: T
authors.lastname: Inokuma
authors.affiliation: Institute of Biomedical Sciences and Graduate School of Pharmaceutical Sciences, Tokushima University, 1-78-1 Shomachi, Tokushima, 770-8505, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Otaka
mesh_terms: D000818:Animals; D006801:Humans; D010455:Peptides / Q000737:chemistry* / Q000378:metabolism; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism
chemical_list: D010455:Peptides; D011506:Proteins
keywords: Spr; amide bond cleavage; artificial amino acid; peptide bond cleavage; stimulus responsive; stimulus-responsive peptide-bond-cleaving residue; trimethyl lock