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.
Cren
Sylvaine
S
School of Chemistry, Centre for Biomolecular Sciences, University of Nottingham, University Park, Nottingham, UKNG7 2RD.
Gurcha
Sudagar S
SS
Blake
Alexander J
AJ
Besra
Gurdyal S
GS
Thomas
Neil R
NR
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