Bacteria Hunt Bacteria through an Intriguing Cyclic Peptide

Abstract

In the last few decades, peptides have been victorious over small molecules as therapeutics due to their broad range of applications, high biological activity, and high specificity. However, the main challenges to overcome if peptides are to become effective drugs is their low oral bioavailability and instability under physiological conditions. Cyclic peptides play a vital role in this context because they show higher stability under physiological conditions, higher membrane permeability, and greater oral bioavailability than that of their corresponding linear analogues. In this regard, cyclic antimicrobial peptides (AMPs) have gained considerable attention in the field of novel antibiotic development. Bacterial strains produce cyclic AMPs through two pathways: ribosomal and nonribosomal. This review provides an overview of the chemical classification of cyclic AMPs isolated from bacteria, and provides a description of their biological activity and mode of action.

Antimicrobial peptides – Advances in development of therapeutic applications

“…Peptide cyclization with limited conformational flexibility not only provides large surface area, which could enhance membrane-binding affinity but also prevents protease degradation. Until now, there are three common types of cross-linking construction: All-hydrocarbon stapling system [ 184 , 185 ], disulfide bonds and its modification [ [186] , [187] , [188] , [189] ] and lactam-bridge [ [190] , [191] , [192] ] ( Fig. 4 ).…”

Short Cationic Peptidomimetic Antimicrobials

“…These peptides adopt a loop formation with one disulfide bridge [15]. There are also cyclic AMPs such as gramicidin S [16].…”

“…Small-molecule peptidomimetics and glycopeptide antibiotics have been reviewed by Ghosh and Haldar [67,68] including a recent review on bacteriophages as alternatives for conventional antibiotics [69]. Abdel Monaim et al recently published a review on cyclic AMPs [16] as effective antibacterials. From the key structural features of natural AMPs, peptidomimetic molecules possess an amphiphilic backbone and net positive charge that helps to mimic the biological function of AMPs.…”

Design, Engineering and Discovery of Novel α-Helical and β-Boomerang Antimicrobial Peptides against Drug Resistant Bacteria

“…Proteolytic degradation is likely to be the major cause of the short in vivo half-life of AMPs. Several strategies have been exploited for the generation of AMPs that are stable against proteases: e.g., cyclization of AMPs [56] and the introduction of disulfide bonds and covalent bonds between sidechains [57][58][59]. Alternative approaches to minimize proteolytic cleavage include producing synthetic AMPs that incorporate D-amino acids [60], β-amino acids [61], and other non-natural amino acids [62].…”