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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.