Photo-induced synthesis, stereochemistry and antitumor activity of valine-based small cyclopeptides

Abstract

The development of cyclic peptides has become a significant research direction due to their unique structural features. The spatial structure of small cyclopeptides greatly affects their biological activity. This study has presented the design and synthesis of a series of chiral valine-based cyclopeptides by the intramolecular photoinduced single electron transfer cyclization reaction (IPETC). A stereochemical study by combining ECD spectroscopy with theoretical calculations has revealed that the C-3 centers in most cyclopeptides exhibit opposite configurations to those of Val² in cyclic skeletons, suggesting that the C-3 configurations are strongly affected by the chirality of the Val² residue. Bioactive assays have shown that a cyclotetrapeptide 7 with three pure L-valine residues exhibits moderate antitumor activity against HepG-2 cells. Thus, this paper has provided some unique information on the chirality and bioactivity of small cyclopeptides with isoindolinone, and may be useful for further drug design based on cyclopeptides.