The in vitro screening of stereoisomeric bicyclic peptidomimetics towards SAP2 of Candida albicans revealed a constrained chemotype as aspartic protease inhibitor in the micromolar to nanomolar range. The results indicated that the acetal bridge may serve as a transition-state isostere, and that the right match between interactions with subsites and the orientation by hydrogen bonding with Gly85 is the main requisite for inhibitory activity. Molecular docking calculations suggested the bicyclic acetal scaffold to be capable of interacting with the two catalytic aspartic acids, thus resulting in good inhibitory activity with only two hydrophobic groups addressing the enzyme catalytic subsites.

Bicyclic Peptidomimetics Targeting Secreted Aspartic Protease 2 (SAP2) from Candida albicans Reveal a Constrained Inhibitory Chemotype / C. Calugi; A. Trabocchi; F. De Bernardis; S. Arancia; P. Navarra; R. Cauda; A. Cassone; A. Guarna. - In: BIOORGANIC & MEDICINAL CHEMISTRY. - ISSN 0968-0896. - STAMPA. - 20:(2012), pp. 7206-7213. [10.1016/j.bmc.2012.09.031]

Bicyclic Peptidomimetics Targeting Secreted Aspartic Protease 2 (SAP2) from Candida albicans Reveal a Constrained Inhibitory Chemotype

CALUGI, CHIARA;TRABOCCHI, ANDREA;GUARNA, ANTONIO
2012

Abstract

The in vitro screening of stereoisomeric bicyclic peptidomimetics towards SAP2 of Candida albicans revealed a constrained chemotype as aspartic protease inhibitor in the micromolar to nanomolar range. The results indicated that the acetal bridge may serve as a transition-state isostere, and that the right match between interactions with subsites and the orientation by hydrogen bonding with Gly85 is the main requisite for inhibitory activity. Molecular docking calculations suggested the bicyclic acetal scaffold to be capable of interacting with the two catalytic aspartic acids, thus resulting in good inhibitory activity with only two hydrophobic groups addressing the enzyme catalytic subsites.
2012
20
7206
7213
C. Calugi; A. Trabocchi; F. De Bernardis; S. Arancia; P. Navarra; R. Cauda; A. Cassone; A. Guarna
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Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/710731
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