Silanediol-based Inhibitor of Thermolysin

Overview

Journal Bioorg Med Chem Lett

Specialty Biochemistry

Date 2002 Nov 22

PMID 12443790

Citations 7

Authors

Jaeseung Kim

Athanasios Glekas

Scott McN Sieburth

Affiliations

Soon will be listed here.

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).

Citing Articles

The role of silicon in drug discovery: a review.

Panayides J, Riley D, Hasenmaile F, van Otterlo W RSC Med Chem. 2024; 15(10):3286-3344.

PMID: 39430101 PMC: 11484438. DOI: 10.1039/d4md00169a.

Efficient Entropy-Driven Inhibition of Dipeptidyl Peptidase III by Hydroxyethylene Transition-State Peptidomimetics.

Ivkovic J, Jha S, Lembacher-Fadum C, Puschnig J, Kumar P, Reithofer V Chemistry. 2021; 27(56):14108-14120.

PMID: 34314529 PMC: 8518066. DOI: 10.1002/chem.202102204.

On the Potential of Silicon as a Building Block for Life.

Petkowski J, Bains W, Seager S Life (Basel). 2020; 10(6).

PMID: 32532048 PMC: 7345352. DOI: 10.3390/life10060084.

Study of the chelating properties of Ge(OH)2 functionality as metal binding group for Zn2+ cation in simplified protease-like environments: a DFT analysis.

Rodriguez Ortega P, Montejo M, Lopez Gonzalez J J Mol Model. 2014; 20(9):2430.

PMID: 25142338 DOI: 10.1007/s00894-014-2430-2.

Quantum chemical study of silanediols as metal binding groups for metalloprotease inhibitors.

Ignatyev I, Montejo M, Rodriguez Ortega P, Lopez Gonzalez J J Mol Model. 2013; 19(4):1819-34.

PMID: 23315215 DOI: 10.1007/s00894-012-1745-0.