Synthesis and biological evaluation of new inhibitors of UDP-Galf transferase--a key enzyme in M. tuberculosis cell wall biosynthesis.
Two iminosugars have been designed and synthesized as potential inhibitors of UDP-Galf transferase, an enzyme involved in Mycobacterium tuberculosis cell wall biosynthesis. The design is based on a proposed model of the transition state for the transferase reaction. One of the two racemic compounds is the first reported inhibitor of the target enzyme from M. smegmatis.
School of Chemistry, Centre for Biomolecular Sciences, University of Nottingham, University Park, Nottingham, UKNG7 2RD.
Sylvaine
S
Cren
Sudagar S
SS
Gurcha
Alexander J
AJ
Blake
Gurdyal S
GS
Besra
Neil R
NR
Thomas
D002384:Catalysis; D002473:Cell Wall / Q000187:drug effects / Q000378:metabolism; D004353:Drug Evaluation, Preclinical; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D005685:Galactans / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D005700:Galactosyltransferases / Q000037:antagonists & inhibitors* / Q000096:biosynthesis* / Q000737:chemistry; D007097:Imines / Q000138:chemical synthesis / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D008968:Molecular Conformation; D020102:Mycobacterium smegmatis / Q000187:drug effects / Q000378:metabolism; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000201:enzymology*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013379:Substrate Specificity
D004791:Enzyme Inhibitors; D005685:Galactans; D007097:Imines; D005700:Galactosyltransferases