SAR directed design and synthesis of novel beta(1-4)-glucosyltransferase inhibitors and their in vitro inhibition studies.
This paper describes SAR directed design and synthesis of novel beta(1-4)-glucosyltransferase (BGT) inhibitors. The designed inhibitors 1-5 provide conformational mimicry of the transition-state in glucosyltransfer reactions. The compounds were tested for in vitro inhibitory activity against (BGT) and the inhibition kinetics were examined. Three of the designed molecules were found to be potential inhibitors of BGT having IC50 values in micromolar (microM) range. Useful structure-activity relationships were established, which provide guidelines for the design of future generations of inhibitors of BGT.
Bhattacharya
Asish K
AK
Fachbereich Chemie, Universität Konstanz, Fach M725, D-78457, Konstanz, Germany.
Stolz
Florian
F
Kurzeck
Jürgen
J
Rüger
Wolfgang
W
Schmidt
Richard R
RR
D017122:Bacteriophage T4 / Q000201:enzymology; D020134:Catalytic Domain; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D005964:Glucosyltransferases / Q000037:antagonists & inhibitors*; D020128:Inhibitory Concentration 50; D007700:Kinetics; D018716:Molecular Mimicry; D011849:Radioactive Tracers; D013329:Structure-Activity Relationship; D014530:Uridine Diphosphate / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology
D004791:Enzyme Inhibitors; D011849:Radioactive Tracers; D014530:Uridine Diphosphate; D005964:Glucosyltransferases