Synthesis and Molecular Modeling Studies of Derivatives of a Highly Potent Peptidomimetic Vinyl Ester as Falcipain-2 Inhibitors
Articolo
Data di Pubblicazione:
2012
Citazione:
Synthesis and Molecular Modeling Studies of Derivatives of a Highly Potent Peptidomimetic Vinyl Ester as Falcipain-2 Inhibitors / R. Ettari, N. Micale, G. Grazioso, F. Bova, T. Schirmeister, S. Grasso, M. Zappalà. - In: CHEMMEDCHEM. - ISSN 1860-7179. - 7:9(2012), pp. 1594-1600.
Abstract:
Herein we report the synthesis of a set of constrained peptidomimetics endowed with an electrophilic vinyl ester warhead and structurally related to a previously identified lead compound, a potent and irreversible inhibitor of falcipain-2 (FP-2). FP-2 is the main hemoglobinase of the malaria parasite P.falciparum. The new compounds were evaluated for their inhibition against FP-2, and the results were rationalized on the basis of docking experiments. These studies underscore the pivotal role of both the ester function at the P1' site and the trifluoromethyl group of the P3 side chain in determining the correct orientation of the Michael acceptor warhead in the catalytic site, and as a consequence, the potency of the inhibitors as well as their reversible or irreversible mode of inhibition.
Tipologia IRIS:
01 - Articolo su periodico
Keywords:
cysteine proteases; docking; falcipain-2; inhibitors; peptidomimetics
Elenco autori:
R. Ettari, N. Micale, G. Grazioso, F. Bova, T. Schirmeister, S. Grasso, M. Zappalà
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