In this work we reported the generation of D-proline-derived hydroxamic acids as inhibitors of anthrax lethal factor (LF), taking advantage of a pyrrolidine ring as the central scaffold and a hydroxamate group as the Zn2+ chelating agent. The introduction of two hydrophobic groups addressing the S10 subsite and a long substrate-binding groove was conceived by overlapping the bioactive conformations of two reported LF inhibitors. Micromolar affinity of compound 38 suggested cis-3-substituted-1-sulfonamido-D-proline hydroxamic acids as a promising class of peptidomimetic inhibitors for developing novel LF inhibitors.

D-Proline-based peptidomimetic inhibitors of anthrax lethal factor / Calugi, Chiara; Trabocchi, Andrea; Lalli, C.; Guarna, Antonio. - In: EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY. - ISSN 0223-5234. - STAMPA. - 56:(2012), pp. 96-107. [10.1016/j.ejmech.2012.08.028]

D-Proline-based peptidomimetic inhibitors of anthrax lethal factor

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

Abstract

In this work we reported the generation of D-proline-derived hydroxamic acids as inhibitors of anthrax lethal factor (LF), taking advantage of a pyrrolidine ring as the central scaffold and a hydroxamate group as the Zn2+ chelating agent. The introduction of two hydrophobic groups addressing the S10 subsite and a long substrate-binding groove was conceived by overlapping the bioactive conformations of two reported LF inhibitors. Micromolar affinity of compound 38 suggested cis-3-substituted-1-sulfonamido-D-proline hydroxamic acids as a promising class of peptidomimetic inhibitors for developing novel LF inhibitors.
2012
56
96
107
Calugi, Chiara; Trabocchi, Andrea; Lalli, C.; Guarna, Antonio
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Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/710727
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