Work

Divergent Modes of Enzyme Inhibition in a Homologous Structure−Activity Series

Year: 2009

Type: article

Abstract: A docking screen identified reversible, noncovalent inhibitors (e.g., 1) of the parasite cysteine protease cruzain. Chemical optimization of 1 led to a series of oxadiazoles possessing interpretable SAR and potencies as much as 500-fold greater than 1. Detailed investigation of the SAR series subsequently revealed that many members of the oxadiazole class (and surprisingly also 1) act via divergent modes of inhibition (competitive or via colloidal aggregation) depending on the assay conditions employed.

Source: Journal of Medicinal Chemistry

DOI: 10.1021/jm9009229

Authors: Rafaela S. Ferreira, Clifford Bryant, Kenny K. H. Ang, James H. McKerrow, Brian K. Shoichet, Adam R. Renslo

Institution: University of California, San Francisco

Language: English

Topic: Trypanosoma species research and implications

Subfield: Epidemiology

Field: Medicine

Domain: Health Sciences

Open Access status: green

Funder: National Institute of General Medical Sciences

Award: A Specific Mechanism for non-specific inhibition