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Lookup NU author(s): Professor Del Besra
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The biochemically unique structures of sugar residues in the outer cell wall of Mycobacterium tuberculosis (MTB) make the pathways for their biosynthesis and utilization attractive targets for the development of new and selective anti-tubercular agents. A cell-free assay system for galactosyltransferase activity using UDP[14C]Gal as the glycosyl donor, as well as an in vitro colorimetric broth micro-dilution assay system, were used to determine the activities of three β-D-gal(f)(1→4)-α-L-rham(p) octyl disaccharides as substrates and antimycobacterial agents respectively. The cell-free enzymatic studies using compounds 8 and 10 suggested that these disaccharides bind to and are effective substrates for a putative mycobacterial galactosyltransferase. The modified acceptor 8 was found to be a slower but prolonged binder as compared to the less substituted analogue 10 as evidenced by their K(m) and V(max) values. Moderate antimycobacterial activity was observed with compounds 8 and 9 against MTB H37Ra and three clinical isolates of Mycobacterium avium complex (MAC). (C) 1999 Elsevier Science Ltd.
Author(s): Pathak AK, Besra GS, Crick D, Maddry JA, Morehouse CB, Suling WJ, Reynolds RC
Publication type: Article
Publication status: Published
Journal: Bioorganic and Medicinal Chemistry
ISSN (print): 0968-0896
ISSN (electronic): 1464-3391
PubMed id: 10632050
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