Synthesis of silanediol-based protease inhibitors

ORGN 429

Wondwossen D. Arasho,, Madhusudhan Purushotham,, Sushmita Sen,, and Scott McN. Sieburth, Department of Chemistry, Temple University, 1901 N. 13th Street, Philadelphia, PA 19122

Silanediol-based peptide mimics have been found to be low nanomolar inhibitors of metallo and aspartic proteases.  Development of these inhibitors is dependent on the efficient assembly of the silane structures with full control of stereochemistry.  We have developed a new set of chemistry that delivers key intermediates in enantiomerically pure form.  The application of this chemistry to the preparation of inhibitors of anthrax lethal factor and angiotensin-converting enzyme (both metalloproteases) will be described. 




Bioorganic, Metal-Mediated Reactions, and Molecular Recognition
8:00 PM-10:00 PM, Tuesday, 30 August 2005 Washington DC Convention Center -- Hall A, Poster

8:00 PM-10:00 PM, Monday, 29 August 2005 Washington DC Convention Center -- Hall A, Sci-Mix

Division of Organic Chemistry

The 230th ACS National Meeting, in Washington, DC, Aug 28-Sept 1, 2005