7os8

Publication Abstract from PubMed

The pharmacodynamic and pharmacokinetic properties of bioactive peptides can be modulated by introducing conformational constraints such as intramolecular macrocyclizations, which can involve either the backbone and/or side chains. Herein, we aimed at increasing the alpha-helicity content of temporin L, an isoform of an intriguing class of linear antimicrobial peptides (AMPs), endowed with a wide antimicrobial spectrum, by the employment of diverse side-chain tethering strategies, including lactam, 1,4-substituted [1,2,3]-triazole, hydrocarbon, and disulfide linkers. Our approach resulted in a library of cyclic temporin L analogues that were biologically assessed for their antimicrobial, cytotoxic, and antibiofilm activities, leading to the development of the first-in-class cyclic peptide related to this AMP family. Our results allowed us to expand the knowledge regarding the relationship between the alpha-helical character of temporin derivatives and their biological activity, paving the way for the development of improved antibiotic cyclic AMP analogues.

First-in-Class Cyclic Temporin L Analogue: Design, Synthesis, and Antimicrobial Assessment.,Bellavita R, Casciaro B, Di Maro S, Brancaccio D, Carotenuto A, Falanga A, Cappiello F, Buommino E, Galdiero S, Novellino E, Grossmann TN, Mangoni ML, Merlino F, Grieco P J Med Chem. 2021 Jul 23. doi: 10.1021/acs.jmedchem.1c01033. PMID:34296619^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.