KALLIKREIN INHIBITORS BY GENETIC ENGINEERING

Award Information
Agency:
Department of Health and Human Services
Branch
n/a
Amount:
$50,000.00
Award Year:
1989
Program:
SBIR
Phase:
Phase I
Contract:
n/a
Award Id:
11268
Agency Tracking Number:
11268
Solicitation Year:
n/a
Solicitation Topic Code:
n/a
Solicitation Number:
n/a
Small Business Information
1885 33rd St, Boulder, CO, 80301
Hubzone Owned:
N
Minority Owned:
N
Woman Owned:
N
Duns:
n/a
Principal Investigator:
() -
Business Contact:
() -
Research Institution:
n/a
Abstract
THE AIM OF THIS RESEARCH IS TO PRODUCE INHIBITORS OF HUMAN KALLIKREINS THAT BLOCK KALLIKREIN-MEDIATED CONVERSION OF KININOGENS INTO KININS. KININS ARE IMPLICATED IN THE SYMPTOMS OF ALLERGIC RHINITIS, ASTHMA, AND RHINOVIRUS INFECTION, AND KALLIKREIN INHIBITORS SHOULD BE EFFECTIVE IN AMELIORATING SYMPTOMS ASSOCIATED WITH THESE RESPIRATORY CONDITIONS. IN THIS PHASE I FEASIBILITY STUDY, KALLIKREIN INHIBITORS WILL BE MADE BY MUTAGENESIS OF SECRETORY LEUKOCYTE PROTEASE INHIBITOR AND WILL BE ISOLATED BY SCREENING A YEAST EXPRESSION LIBRARY FOR CLONES THAT BIND KALLIKREINS. THE FIRST-GENERATION INHIBITORS WILL BE (1) SEQUENCED TO DETERMINE THE NATURE OF THEIR AMINO ACID SUBSTITUTIONS, (2) PRODUCED IN SMALL QUANTITIES IN ESCHERICHIA COLI, AND (3) ASSAYED FOR THEIR ABILITIES TO INHIBIT KALLIKREINS. DURING EARLY PHASE II RESEARCH, SUBSEQUENT ROUNDS OF MUTAGENESIS WILL BE CONDUCTED ON PROMISING INHIBITOR VARIANTS TO INCREASE THE SPECIFICITY FOR AND INHIBITION OF KALLIKREINS. THE BEST INHIBITORS WILL BE PRODUCED IN LARGE AMOUNTS AND EVALUATED IN ANIMAL MODELS OF RESPIRATORY DISEASE. THE IN SITU SCREENING METHODOLOGY USED TO DETECT VARIANTS WITH ALTERED PROTEASE-BINDING SPECIFICITY SHOULD BE GENERALLY APPLICABLE FOR MODIFYING THE SPECIFICITY OF ANY RECOMBINANT PROTEASE INHIBITOR.

* information listed above is at the time of submission.

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