title: A silanediol inhibitor of the metalloprotease thermolysin: synthesis and comparison with a phosphinic acid inhibitor.
abstract: A silanediol inhibitor of the metalloprotease thermolysin was prepared for comparison to a known phosphinic acid inhibitor, providing the first comparison of these second-row element based transition-state analogues. Inhibition of thermolysin by the silanediol (K(i) = 41 nM) was comparable to that of the phosphinic acid (K(i) = 10 nM) even though the silanediol is uncharged and thereby lacks the intrinsic Coulombic attraction of the phosphinate anion to the active-site zinc cation. This silanediol protease inhibitor is the least sterically encumbered example prepared to date and, therefore, the most prone toward polymerization. Hydrolysis of a difluorosilane intermediate to the silanediol leads cleanly to a monomeric product.
authors.affiliation: Department of Chemistry, State University of New York at Stony Brook, Stony Brook, New York 11794-3400, USA.
authors.forename: Jaeseung
authors.initials: J
authors.lastname: Kim
authors.forename: Scott McN
authors.initials: SM
authors.lastname: Sieburth
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000737:chemistry; D001665:Binding Sites; D002412:Cations; D017320:HIV Protease Inhibitors / Q000737:chemistry; D006868:Hydrolysis; D057927:Hydrophobic and Hydrophilic Interactions; D010721:Phosphinic Acids / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry; D011480:Protease Inhibitors / Q000138:chemical synthesis / Q000737:chemistry*; D012821:Silanes / Q000138:chemical synthesis / Q000737:chemistry*; D013329:Structure-Activity Relationship; D013820:Thermolysin / Q000037:antagonists & inhibitors*; D015032:Zinc / Q000737:chemistry
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D002412:Cations; D017320:HIV Protease Inhibitors; D010721:Phosphinic Acids; D011108:Polymers; D011480:Protease Inhibitors; D012821:Silanes; C475536:silanediol; D013820:Thermolysin; D015032:Zinc