Improvement on Permeability of Cyclic Peptide/Peptidomimetic: Backbone N-Methylation as A Useful Tool

• Published in: Marine drugs Vol. 19; no. 6; p. 311
• Main Authors: Li, Yang, Li, Wang, Xu, Zhengshuang
• Format: Journal Article
• Language: English
• Published: Basel MDPI AG 27.05.2021; MDPI
• Subjects: Backbone; backbone N-Methylation; Binding sites; Bioavailability; Cell permeability; cyclic peptide; cyclic peptidomimetic; Drug development; Drugs; Hydrogen bonds; Membranes; Methylation; Monoclonal antibodies; Peptides; Peptidomimetics; Permeability; Pharmaceutical industry; Pharmacokinetics; Proteins; Review
• ISSN: 1660-3397; 1660-3397
• DOI: 10.3390/md19060311

Peptides have a three-dimensional configuration that can adopt particular conformations for binding to proteins, which are well suited to interact with larger contact surface areas on target proteins. However, low cell permeability is a major challenge in the development of peptide-related drugs. In recent years, backbone N-methylation has been a useful tool for manipulating the permeability of cyclic peptides/peptidomimetics. Backbone N-methylation permits the adjustment of molecule’s conformational space. Several pathways are involved in the drug absorption pathway; the relative importance of each N-methylation to total permeation is likely to differ with intrinsic properties of cyclic peptide/peptidomimetic. Recent studies on the permeability of cyclic peptides/peptidomimetics using the backbone N-methylation strategy and synthetic methodologies will be presented in this review.