title: Studies on beta-D-Gal(f)-(1-->4)-alpha-L-Rha(p) octyl analogues as substrates for mycobacterial galactosyl transferase activity.
abstract: 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 beta-D-gal(f)(1-->4)-alpha-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 Km and Vmax values. Moderate antimycobacterial activity was observed with compounds 8 and 9 against MTB H37Ra and three clinical isolates of Mycobacterium avium complex (MAC).
authors.affiliation: Department of Organic Chemistry, Southern Research Institute, Birmingham, AL 35255, USA.
authors.forename: A K
authors.initials: AK
authors.lastname: Pathak
authors.forename: G S
authors.initials: GS
authors.lastname: Besra
authors.forename: D
authors.initials: D
authors.lastname: Crick
authors.forename: J A
authors.initials: JA
authors.lastname: Maddry
authors.forename: C B
authors.initials: CB
authors.lastname: Morehouse
authors.forename: W J
authors.initials: WJ
authors.lastname: Suling
authors.forename: R C
authors.initials: RC
authors.lastname: Reynolds
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology*; D000995:Antitubercular Agents / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology*; D002240:Carbohydrate Sequence; D003124:Colorimetry; D004187:Disaccharides / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005700:Galactosyltransferases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D009162:Mycobacterium avium / Q000187:drug effects*; D009169:Mycobacterium tuberculosis / Q000187:drug effects*; D013379:Substrate Specificity
chemical_list: D000900:Anti-Bacterial Agents; D000995:Antitubercular Agents; D004187:Disaccharides; D004791:Enzyme Inhibitors; C403508:SRI 9542; C403509:SRI 9551; D005700:Galactosyltransferases