Silanediol-based inhibitor of thermolysin

Bioorg Med Chem Lett. 2002 Dec 16;12(24):3625-7. doi: 10.1016/s0960-894x(02)00804-1.

Abstract

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).

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Binding, Competitive
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / pharmacology
  • Hydrophobic and Hydrophilic Interactions
  • Phosphinic Acids / chemistry
  • Silanes / chemistry*
  • Thermolysin / antagonists & inhibitors*

Substances

  • Enzyme Inhibitors
  • Phosphinic Acids
  • Silanes
  • silanediol
  • Thermolysin