Revisiting 310-helices: biological relevance, mimetics and applications

Abstract

310-Helices represent the third most abundant secondary structure proteins. Although understandably overshadowed by α-helices for decades, the 310-helix structure is slowly regaining certain relevance in protein science. The key role of this secondary structure in biological processes has been highlighted in reports over the last decade. In addition, 310-helices are considered key intermediates in protein folding as well as a crucial structure for the antimicrobial activity of naturally occurring peptaibols. Thus, it is clear that 310-helices are relevant scaffolds to take into consideration in the field of biomimetics. In this context, this review covers the strategies developed to stabilize the 310-helix structure in peptide chains, from the incorporation of constrained amino acids to stapling methodologies. In the last section, the use of 310-helices as scaffolds of interest in the development of bioactive compounds, catalysts for enantioselective reactions, supramolecular receptors, and membrane-embedded signal transducers are discussed. The present work aims to highlight the relevance, sometimes underestimated, of 310-helices in chemical biology and protein science, providing the tools to develop functional biomimetics with a wide range of potential applications.