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Studies on (beta,1 -> 5) and (beta,1 -> 6) linked octyl Gal(f) disaccharides as substrates for mycobacterial galactosyltransferase activity

Lookup NU author(s): Dr Sudagar Gurcha, Professor Del Besra

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Abstract

The emergence of multi-drug resistant (MDR) strains of Mycobacterium tuberculosis (MTB) and the continuing pandemic of tuberculosis emphasizes the urgent need for the development of new, anti-tubercular agents with novel drug targets. The recent structural elucidation of the mycobacterial cell wall highlights a large variety of structurally unique components that may be a basis for new drug development. This publication describes the synthesis, characterization, and screening of several octyl Galf(beta ,1 -->5)Galf and octyl Galf(beta ,1 -->6)Galf derivatives. A cell-free assay system has been utilized for galactosyltransferase activity using UDP[C-14]Galf as the glycosyl donor, and in vitro inhibitory activity has been determined in a colorimetric broth microdilution assay system against MTB H37Ra and three clinical isolates of Mycobacterium avium complex (MAC). Certain derivatives showed moderate activities against MTB and MAC. The biological evaluation of these disaccharides suggests that more hydrophobic analogues with a blocked reducing end showed better activity as compared to totally deprotected disaccharides that more closely resemble the natural substrates in cell wall biosynthesis. (C) 2001 Elsevier Science Ltd. All rights reserved.


Publication metadata

Author(s): Pathak AK, Pathak V, Seitz L, Maddry JA, Gurcha SS, Besra GS, Suling WJ, Reynolds RC

Publication type: Article

Publication status: Published

Journal: Bioorganic & Medicinal Chemistry

Year: 2001

Volume: 9

Issue: 12

Pages: 3129-3143

ISSN (print):

ISSN (electronic): 1464-3391

Publisher: Pergamon

URL: http://dx.doi.org/10.1016/S0968-0896(01)00179-1

DOI: 10.1016/S0968-0896(01)00179-1


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Funding

Funder referenceFunder name
CA-13148NCI NIH HHS
N01 AI095364NIAID NIH HHS
R01 AI045317NIAID NIH HHS
R01AI45317NIAID NIH HHS

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