Structure – Bioactivity Relationship in Cyclic Peptoids: An Overview

• Published in: European journal of organic chemistry 2022-10, Vol.2022 (38), p.n/a
• Main Author: D'Amato, Assunta
• Format: Article
• Language: English
• Subjects: Bioactive compounds; Biological activity; Biomimetics; Chelation; Glycosidases; Macrocycles; Peptidomimetics; Peptoids; Pharmaceutical chemistry
• ISSN: 1434-193X; 1099-0690
• DOI: 10.1002/ejoc.202200665

Cyclic N‐substituted glycines oligomers, also known as cyclic peptoids, constitute a promising class of novel peptidomimetics, capable of simulating bioactive effectors with enhanced proteolytical stability and cell permeability as crucial bonuses. The macrocyclic constraint, essential for the induction of stable secondary structures, determines the biomimetic potential of such molecules, which act as antimicrobials, cytotoxic agents, siderophores, glycosidases inhibitors and so on. The bioactivity can be either attributed to the macrocyclic core (especially chelation) or to the side‐chains (when endowed with specific groups or pharmacophores). The structure‐bioactivity correlations emerging for this class of peptidomimetics, based on the study of conformational order and morphology of the backbone architecture, unravel interesting avenues for the rational design of more effective cyclooligomeric biomimics. Macrocyclic peptoids display remarkable biological activity thanks to their constitution and functionalization. This Review provides a systematic description of the bioactivities discovered so far, together with a complete structure‐function relationship rationalization. Utilizing a strategic design for the synthesis of cyclic peptoids represents the starting point for further developments of these peptidomimetics as drug candidates.