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 α-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 α-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, T. N.; Mangoni, M. L.; Merlino, F.; Grieco, P.. - In: JOURNAL OF MEDICINAL CHEMISTRY. - ISSN 0022-2623. - 64:15(2021), pp. 11675-11694. [10.1021/acs.jmedchem.1c01033]

First-in-class cyclic Temporin L analogue: design, synthesis, and antimicrobial assessment

Casciaro B.;Cappiello F.;Mangoni M. L.;
2021

Abstract

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 α-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 α-helical character of temporin derivatives and their biological activity, paving the way for the development of improved antibiotic cyclic AMP analogues.
temporin L; cyclic peptides
01 Pubblicazione su rivista::01a Articolo in rivista
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, T. N.; Mangoni, M. L.; Merlino, F.; Grieco, P.. - In: JOURNAL OF MEDICINAL CHEMISTRY. - ISSN 0022-2623. - 64:15(2021), pp. 11675-11694. [10.1021/acs.jmedchem.1c01033]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1579528
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