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ENGINEERING OF THE RECEPTOR-BINDING REGION OF UPA

Award Information

Agency:
Department of Health and Human Services
Branch:
N/A
Award ID:
13878
Program Year/Program:
1990 / SBIR
Agency Tracking Number:
13878
Solicitation Year:
N/A
Solicitation Topic Code:
N/A
Solicitation Number:
N/A
Small Business Information
C-MOTION, INC.
C-MOTION, INC. 15821A CRABBS BRANCH WAY ROCKVILLE, MD 20855
View profile »
Woman-Owned: No
Minority-Owned: No
HUBZone-Owned: No
 
Phase 1
Fiscal Year: 1990
Title: ENGINEERING OF THE RECEPTOR-BINDING REGION OF UPA
Agency: HHS
Contract: N/A
Award Amount: $50,000.00
 

Abstract:

UROKINASE-TYPE PLASMINOGEN ACTIVATOR (UPA) IS A THROMBOLYTICPROTEASE THAT HAS BEEN IMPLICATED IN CERTAIN NONTHROMBOLYTICPHYSIOLOGICAL PROCESSES, MOST NOTABLY THE INVASIVE GROWTH OR MIGRATION OF METASTATIC CELLS AND OF MACROPHAGES. THE ROLE OF UPA IN CELL MIGRATION APPEARS TO INVOLVE BINDING OF THIS PROTEASE TO SPECIFIC CELL SURFACE RECEPTORS. IT IS HOPED TO ENGINEER UPA-DERIVED MOLECULES THAT ARE PROTEOLYTICALLY INACTIVE AND BIND WITH ENHANCED AVIDITY TO THE UPA RECEPTOR. THESE MOLECULES MAY SERVE AS COMPETITIVE INHIBITORS OF NATIVE UPA RECEPTOR BINDING AND IN THIS WAY BEUSEFUL THERAPEUTIC AGENTS BY INHIBITING PHYSIOLOGICAL PROCESSES REQUIRING RECEPTOR-BOUND UPA. IN PHASE I, A UPA-RECEPTOR-BINDING ASSAY WILL BE DEVELOPED. THIS ASSAY WILL INVOLVE YEAST SECRETION OF UPA MOLECULES ONTO NITROCELLULOSE FILTERS AND PROBING OF THESE FILTERS WITH (125)I-LABELED, PURIFIED RECEPTOR MOLECULES. THE ASSAYWILL BE DESIGNED TO BE USED IN PHASE II FOR RAPID SCREENING OF YEAST COLONIES SECRETING UPA MOLECULES THAT HAVE ALTERED RECEPTOR BINDING. A LIBRARY OF VECTORS WITH MUTATIONS WITHIN THE CDNA ENCODING THE RECEPTOR-BINDING REGION OF UPA WILL BE CONSTRUCTED IN ESCHERICHIA COLI. PHASE II WILL INCLUDE SCREENING THIS LIBRARY, FOLLOWING STRATEGIES LEADING TO THE ENGINEERING OF UPA MOLECULES WITH ENHANCED RECEPTOR BINDING, AND TESTING THE ABILITY OF THESE MOLECULES TO COMPETITIVELY INHIBIT BINDING BY WILD-TYPE MOLECULES. THE ABILITY OF THESE MOLECULES TO INHIBIT INVASIVE CELL MIGRATION WILL ALSO BE TESTED.

Principal Investigator:

Donald T Moir
6172750004

Business Contact:

Small Business Information at Submission:

Collaborative Research Inc
2 Oak Pk Bedford, MA 01730

EIN/Tax ID: 522053087
DUNS: N/A
Number of Employees: N/A
Woman-Owned: No
Minority-Owned: No
HUBZone-Owned: No