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  • Durrant_JMedChem_2010

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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 Journal/Magazine › Journal article › peer-review

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Computer-aided identification of Trypanosoma brucei uridine diphosphate galactose 4'-epimerase inhibitors: toward the development of novel therapies for African sleeping sickness. / Durrant, Jacob D.; Urbaniak, Michael D.; Ferguson, Michael A. J. et al.
In: Journal of Medicinal Chemistry, Vol. 53, No. 13, 08.07.2010, p. 5025-5032.

Research output: Contribution to Journal/Magazine › Journal article › peer-review

Harvard

Durrant, JD, Urbaniak, MD, Ferguson, MAJ & McCammon, JA 2010, 'Computer-aided identification of Trypanosoma brucei uridine diphosphate galactose 4'-epimerase inhibitors: toward the development of novel therapies for African sleeping sickness', Journal of Medicinal Chemistry, vol. 53, no. 13, pp. 5025-5032. https://doi.org/10.1021/jm100456a

APA

Durrant, J. D., Urbaniak, M. D., Ferguson, M. A. J., & McCammon, J. A. (2010). Computer-aided identification of Trypanosoma brucei uridine diphosphate galactose 4'-epimerase inhibitors: toward the development of novel therapies for African sleeping sickness. Journal of Medicinal Chemistry, 53(13), 5025-5032. https://doi.org/10.1021/jm100456a

Vancouver

Durrant JD, Urbaniak MD, Ferguson MAJ, McCammon JA. Computer-aided identification of Trypanosoma brucei uridine diphosphate galactose 4'-epimerase inhibitors: toward the development of novel therapies for African sleeping sickness. Journal of Medicinal Chemistry. 2010 Jul 8;53(13):5025-5032. doi: 10.1021/jm100456a

Author

Durrant, Jacob D. ; Urbaniak, Michael D. ; Ferguson, Michael A. J. et al. / Computer-aided identification of Trypanosoma brucei uridine diphosphate galactose 4'-epimerase inhibitors : toward the development of novel therapies for African sleeping sickness. In: Journal of Medicinal Chemistry. 2010 ; Vol. 53, No. 13. pp. 5025-5032.

Bibtex

@article{5dfda08dd5ca43919deaa4583e8a85dd,
title = "Computer-aided identification of Trypanosoma brucei uridine diphosphate galactose 4'-epimerase inhibitors: toward the development of novel therapies for African sleeping sickness",
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.",
keywords = "Animals, Cell Line, Cell Proliferation, Drug Design, Enzyme Inhibitors, Humans, Inhibitory Concentration 50, Molecular Dynamics Simulation, Trypanocidal Agents, Trypanosoma brucei brucei, Trypanosomiasis, African, UDPglucose 4-Epimerase",
author = "Durrant, {Jacob D.} and Urbaniak, {Michael D.} and Ferguson, {Michael A. J.} and McCammon, {J. Andrew}",
note = "ACS Author choice under CC-BY",
year = "2010",
month = jul,
day = "8",
doi = "10.1021/jm100456a",
language = "English",
volume = "53",
pages = "5025--5032",
journal = "Journal of Medicinal Chemistry",
issn = "1520-4804",
publisher = "American Chemical Society",
number = "13",

}

RIS

TY - JOUR

T1 - Computer-aided identification of Trypanosoma brucei uridine diphosphate galactose 4'-epimerase inhibitors

T2 - toward the development of novel therapies for African sleeping sickness

AU - Durrant, Jacob D.

AU - Urbaniak, Michael D.

AU - Ferguson, Michael A. J.

AU - McCammon, J. Andrew

N1 - ACS Author choice under CC-BY

PY - 2010/7/8

Y1 - 2010/7/8

N2 - 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.

AB - 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.

KW - Animals

KW - Cell Line

KW - Cell Proliferation

KW - Drug Design

KW - Enzyme Inhibitors

KW - Humans

KW - Inhibitory Concentration 50

KW - Molecular Dynamics Simulation

KW - Trypanocidal Agents

KW - Trypanosoma brucei brucei

KW - Trypanosomiasis, African

KW - UDPglucose 4-Epimerase

U2 - 10.1021/jm100456a

DO - 10.1021/jm100456a

M3 - Journal article

C2 - 20527952

VL - 53

SP - 5025

EP - 5032

JO - Journal of Medicinal Chemistry

JF - Journal of Medicinal Chemistry

SN - 1520-4804

IS - 13

ER -