Titre : Synthesis, Conformational Analysis and Bioactivity Evaluation of Peptaibols.
Endroit : Pavillon Roger-Gaudry, salle G-815 à 11 h.
Hôte : Professeur William Lubell
Cette conférence sera prononcée (en anglais) par la professeure Marta De Zotti du département de chimie de l'Université de Padoue en Italie.
Résumé : Peptaibols are natural antimicrobial peptides that commonly feature a high amount of α-aminoisobutyric acid residues and a C-terminal amino alcohol moiety. Peptaibols possess stable helical structures that are resistant to enzymatic hydrolysis, and exhibit interesting antibiotic and antifungal properties; however, their mechanisms of action are still unknown. We have developed a versatile solid-phase strategy for the synthesis of peptaibols as demonstrated by the preparation of heptaibin, a novel antifungal peptaibol antibiotic. By means of various biophysical techniques, we shed light on their membrane-interaction mechanism. In particular, conformational analysis on short- and medium-length peptaibiotics has been performed in different environments, using FT-IR, CD an 2D-NMR spectroscopy combined with MD calculations, and X-ray crystallography. The influence of structure has been studied on protease resistance, antimicrobial activity, cytotoxicity, and hemolysis. In particular, trichogin analogs were designed showing potent cytotoxicity against tumor cells without affecting healthy cells.
Biographie : Dr. Marta De Zotti received her Ph.D. under the supervision of Professor Claudio Toniolo at the University of Padua, Italy in 2007. As a visiting Ph.D. student (2006) and post-doc fellow (2007), De Zotti studied respectively chiral α-amino acid analysis with Professor H. Brückner (University of Giessen, Germany) and mastered in vitro analysis of antimicrobial agents under the direction of Professor K.-S. Hahm (University of Kwangiu, South Korea). In 2012, as recipient of a Royal Society Fellowship in Chemistry, she conceived new methods for the synthesis of sterically hindered peptides in the laboratory of Professor J. Clayden (University of Manchester, UK). In 2014, she joined the faculty of the Department of Chemistry at the University of Padua as a recipient of a prestigious three-year Future in Research Grant. Co-author of ~60 scientific publications, her research interests focus on the synthesis and conformational analysis of peptaibiotics, using molecular dynamics calculations, and 2D-NMR, FTIR and circular dichroism spectroscopy, to study peptide-membrane interactions and structure-activity relationships influencing enzymatic stability, as well as antimicrobial and anticancer activity.
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