Specific peptide inhibitors of trypanothione reductase with backbone structures unrelated to that of substrate: potential rational drug design lead frameworks

Amino Acids
J H McKieK T Douglas

Abstract

By introducing cationic charge sites novel peptide lead inhibitor structures for trypanothione reductase have been designed using molecular modelling methods. The inhibitors showed reversible, linear competitive inhibition and the strongest peptide inhibitor to date was found to be N-benzyloxycarbonyl-Ala-Arg-Arg-4-methoxy-beta-naphthylamide with a Ki value of 2.4 microM and a selectivity for parasitic enzyme (trypanothione reductase) over the host enzyme (human glutathione reductase) of over 3 orders of magnitude.

Citations

Oct 23, 2013·Future Medicinal Chemistry·Gianni ColottiAndrea Ilari
Oct 23, 2013·Future Medicinal Chemistry·Benjamín Aguilera-VenegasHernán Speisky
Sep 22, 2009·Journal of Molecular Graphics & Modelling·Samuel Silva da Rocha PitaMagaly Girão Albuquerque
Jun 19, 2012·Chemical Biology & Drug Design·Samuel Silva Da Rocha PitaPedro Geraldo Pascutti

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