Different Approaches to Cyclize a Cell-Penetrating Peptide and to Tether Bioactive Payloads

Abstract

Cell-penetrating peptides (CPPs) are versatile tools to deliver various molecules into different cell types. The majority of CPPs are usually represented by linear structures, but numerous recent studies demonstrated cyclization to be an effective strategy leading to favorable biological activities. Here we describe two different methods for the side chain and backbone cyclization of CPPs . Furthermore, we highlight straightforward procedures for the covalent coupling of fluorophores or cytotoxic payloads.

Keywords: Cell-penetrating peptides; Click reaction; Cytotoxic payload; Fluorophore labeling; Head-to-tail cyclization; Oxime ligation; Side chain-to-side chain cyclization.