Home > Research > Publications & Outputs > Computer-aided identification of Trypanosoma br...

Electronic data

  • Durrant_JMedChem_2010

    Rights statement: ACS Author choice under CC-BY

    Final published version, 4 MB, PDF-document

    Available under license: CC BY

Links

Text available via DOI:

View graph of relations

Computer-aided identification of Trypanosoma brucei uridine diphosphate galactose 4'-epimerase inhibitors: toward the development of novel therapies for African sleeping sickness

Research output: Contribution to journalJournal article

Published
Close
<mark>Journal publication date</mark>8/07/2010
<mark>Journal</mark>Journal of Medicinal Chemistry
Issue number13
Volume53
Number of pages8
Pages (from-to)5025-5032
<mark>State</mark>Published
<mark>Original language</mark>English

Abstract

Trypanosoma brucei, the causative agent of human African trypanosomiasis, affects tens of thousands of sub-Saharan Africans. As current therapeutics are inadequate due to toxic side effects, drug resistance, and limited effectiveness, novel therapies are urgently needed. UDP-galactose 4'-epimerase (TbGalE), an enzyme of the Leloir pathway of galactose metabolism, is one promising T. brucei drug target. We here use the relaxed complex scheme, an advanced computer-docking methodology that accounts for full protein flexibility, to identify inhibitors of TbGalE. An initial hit rate of 62% was obtained at 100 microM, ultimately leading to the identification of 14 low-micromolar inhibitors. Thirteen of these inhibitors belong to a distinct series with a conserved binding motif that may prove useful in future drug design and optimization.

Bibliographic note

ACS Author choice under CC-BY