Silanediol-based inhibitor of thermolysin.
The first silanediol inhibitor of thermolysin is reported, prepared by analogy with the Grobelny/Bartlett phosphinate inhibitor. A Cbz group on nitrogen proved to be unstable to the triflic acid mediated silanediol deprotection and was replaced with a dihydrocinnamoyl group. The silanediol was prepared in high purity by hydrolysis of a difluorosilane intermediate and proved to be an effective inhibitor, differing from the phosphinate by a factor of 4 (K(i)=41nM).
Kim
Jaeseung
J
Department of Chemistry, State University of New York at Stony Brook, 11794-3400, USA.
Glekas
Athanasios
A
McN Sieburth
Scott
S
D001667:Binding, Competitive; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D057927:Hydrophobic and Hydrophilic Interactions; D010721:Phosphinic Acids / Q000737:chemistry; D012821:Silanes / Q000737:chemistry*; D013820:Thermolysin / Q000037:antagonists & inhibitors*
D004791:Enzyme Inhibitors; D010721:Phosphinic Acids; D012821:Silanes; C475536:silanediol; D013820:Thermolysin