Yamamoto, Jun Tokushima University
Kohiki, Taiki Tokushima University
artificial amino acid
amide bond cleavage
peptide bond cleavage
stimulus-responsive peptide-bond-cleaving residue
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.
Journal of Peptide Science
European Peptide Society and John Wiley & Sons, Ltd.
This is the peer reviewed version of the following article: Shigenaga, A., Yamamoto, J., Kohiki, T., Inokuma, T., and Otaka, A. (2017) Invention of stimulus‐responsive peptide‐bond‐cleaving residue (Spr) and its application to chemical biology tools. J. Pept. Sci., 23: 505–513. doi: 10.1002/psc.2961. , which has been published in final form at https://doi.org/10.1002/psc.2961. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions.
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