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STRUCTURE-BASE ALDOSE REDUCTASE INHIBITORS

Award Information
Agency: Department of Health and Human Services
Branch: N/A
Contract: N/A
Agency Tracking Number: 19206
Amount: $50,000.00
Phase: Phase I
Program: SBIR
Solicitation Topic Code: N/A
Solicitation Number: N/A
Timeline
Solicitation Year: N/A
Award Year: 1992
Award Start Date (Proposal Award Date): N/A
Award End Date (Contract End Date): N/A
Small Business Information
2190 Parkway Lake Drive
Birmingham, AL 35244
United States
DUNS: N/A
HUBZone Owned: No
Woman Owned: No
Socially and Economically Disadvantaged: No
Principal Investigator
 David W Borhani
 (205) 444-4600
Business Contact
Phone: () -
Research Institution
N/A
Abstract

THE LONG-TERM OBJECTIVE IS TO DESIGN AND DEVELOP POTENT AND HIGHLY SPECIFIC INHIBITORS OF THE ENZYME ALDOSE REDUCTASE. ALDOSE REDUCTASE CATALYZES THE REDUCTION OF GLUCOSE TO SORBITOL. IT HAS BEEN IMPLICATED IN THE PATHOGENESIS OF THE CHRONIC COMPLICATI0NS OF DIABETES MELLITUS. CURRENT INHIBITORS OF THIS ENZYME LACK SPECIFICITY AND POTENCY, AND ARE ASSOCIATED WITH UNDESIRABLE SIDE EFFECTS. BIOCRYST'S EXPERIENCE WITH THE STRUCTURE-BASED DESIGN OF INHIBITORS OF PURINE NUCLEOSIDE PHOSPHORYLASE INDICATES THAT KNOWLEDGE OF THE THREE-DIMENSIONAL STRUCTURE OF A TARGET ENZYME, AND ITS ACTIVE SITE, IS A TREMENDOUS AID TO THE DEVELOPMENT OF INHIBITORS THAT ARE BOTH SAFE AND HIGHLY SPECIFIC. BIOCRYST HAS SOLVED AND REFINED THE X-RAY CRYSTAL STRUCTURE OF PORCINE ALDOSE REDUCTASE APO-ENZYME, AND HAS OBTAINED CRYSTALS AND SOLVED THE STRUCTURES OF BOTH PORCINE AND HUMAN ALDOSE REDUCTASE COMPLEXED WITH ITS COFACTOR NADPH. OUR GOAL IS TO LOCATE AND CHARACTERIZE THE BINDING SITES OF THE ENZYMATIC SUBSTRATE GLUCOSE AND THE BEST EXISTING ALDOSE REDUCTASE INHIBITORS (PHASE I), AND THEN DESIGN AND SYNTHESIZE POTENT AND SPECIFIC INHIBITORS OF THE ENZYME-BASED ON THIS INFORMATION (PHASE II).

* Information listed above is at the time of submission. *

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