In this study we designed and synthesized a new library of antimicrobial peptides correlated to [Pro3,DLeu9]TL 1, a temporin L derivative devoid of cytolytic effects in vitro, and investigated the correlation between the a-helical content of the compounds and their antibacterial, cytotoxic and hemolytic activities. We systematically replaced Gly in position 10 of reference peptide with several amino acids. Structure-activity relationship studies of these analogues were performed by means of antimicrobial and cytotoxicity assays along with CD spectroscopy analyses. NMR analysis was also accomplished for compound 10. As well, the most promising peptides were additionally evaluated for their activity against some clinical strains isolated from human skin and for their mechanism of action by studying the kinetics of membrane perturbation of some representative microbial strains. We identified novel analogues with interesting properties that make them attractive lead compounds for potential topical applications.

Glycine-replaced derivatives of [Pro3,DLeu9]TL, a temporin L analogue: Evaluation of antimicrobial, cytotoxic and hemolytic activities / Merlino, Francesco; Carotenuto, Alfonso; Casciaro, Bruno; Martora, Francesca; Loffredo, Maria Rosa; Di Grazia, Antonio; Yousif, Ali M.; Brancaccio, Diego; Palomba, Luciana; Novellino, Ettore; Galdiero, Massimiliano; Iovene, Maria Rosaria; Mangoni, Maria L.; Grieco, Paolo. - In: EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY. - ISSN 0223-5234. - 139:(2017), pp. 750-761. [10.1016/j.ejmech.2017.08.040]

Glycine-replaced derivatives of [Pro3,DLeu9]TL, a temporin L analogue: Evaluation of antimicrobial, cytotoxic and hemolytic activities

Merlino, Francesco
Co-primo
;
Carotenuto, Alfonso
Co-primo
;
Martora, Francesca;Yousif, Ali M.;Brancaccio, Diego;Novellino, Ettore;Galdiero, Massimiliano;Iovene, Maria Rosaria;Grieco, Paolo
2017

Abstract

In this study we designed and synthesized a new library of antimicrobial peptides correlated to [Pro3,DLeu9]TL 1, a temporin L derivative devoid of cytolytic effects in vitro, and investigated the correlation between the a-helical content of the compounds and their antibacterial, cytotoxic and hemolytic activities. We systematically replaced Gly in position 10 of reference peptide with several amino acids. Structure-activity relationship studies of these analogues were performed by means of antimicrobial and cytotoxicity assays along with CD spectroscopy analyses. NMR analysis was also accomplished for compound 10. As well, the most promising peptides were additionally evaluated for their activity against some clinical strains isolated from human skin and for their mechanism of action by studying the kinetics of membrane perturbation of some representative microbial strains. We identified novel analogues with interesting properties that make them attractive lead compounds for potential topical applications.
2017
Glycine-replaced derivatives of [Pro3,DLeu9]TL, a temporin L analogue: Evaluation of antimicrobial, cytotoxic and hemolytic activities / Merlino, Francesco; Carotenuto, Alfonso; Casciaro, Bruno; Martora, Francesca; Loffredo, Maria Rosa; Di Grazia, Antonio; Yousif, Ali M.; Brancaccio, Diego; Palomba, Luciana; Novellino, Ettore; Galdiero, Massimiliano; Iovene, Maria Rosaria; Mangoni, Maria L.; Grieco, Paolo. - In: EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY. - ISSN 0223-5234. - 139:(2017), pp. 750-761. [10.1016/j.ejmech.2017.08.040]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11588/695278
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