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DEVELOPMENT OF ELASTASE INHIBITORS TO TREAT EMPHYSEMA

Award Information

Agency:
Department of Health and Human Services
Branch:
N/A
Award ID:
16720
Program Year/Program:
1991 / SBIR
Agency Tracking Number:
16720
Solicitation Year:
N/A
Solicitation Topic Code:
N/A
Solicitation Number:
N/A
Small Business Information
MOLECULAR DESIGN INTERNATIONAL, INC.
111 South Highland Street MEMPHIS, TN 38111-
View profile »
Woman-Owned: No
Minority-Owned: No
HUBZone-Owned: No
 
Phase 1
Fiscal Year: 1991
Title: DEVELOPMENT OF ELASTASE INHIBITORS TO TREAT EMPHYSEMA
Agency: HHS
Contract: N/A
Award Amount: $50,000.00
 

Abstract:

THE GOAL OF THIS PROJECT IS TO DEVELOP A SYNTHETIC INHIBITOR OF ELASTASE THAT WILL BE EFFECTIVE AND SAFE IN THE TREATMENT OF EMPHYSEMA. TWO DIFFERENT LABORATORIES REPORTED THAT CHLOROMETHYL KETONE (CMK) IS EFFECTIVE IN ANIMAL MODELS OF EMPHYSEMA. HOWEVER, THE CMK ARE TOO TOXIC FOR HUMAN USE. WE HAVE MODIFIED THE STRUCTURE OF THE CMK TO RETAIN ITS ACTIVITY AND DESIRABLE PHYSICAL PROPERTIES BUT REDUCE ITS TOXICITY. OUR INITIAL INHIBITOR, A DERIVATIVE OF N-CBZ- PHENYLALANINE, KI = 3.61 +/- 0.07 X 10-5 M, WAS EVALUATED AGAINST THE SERINE ENZYME CHYMOTRYPSIN. CMK REACTS WITH GLUTATHIONE LEADING TO TOXIC EFFECTS. OUR INHIBITOR DOES NOT REACT WITH GLUTATHIONE. WE WILL SYNTHESIZE TWO ADDITIONAL INHIBITORS AND COMPARE THEM WITH OUR PRESENT INHIBITOR. AN OLIGOPEPTIDE INHIBITOR WILL BE SYNTHESIZED BASED ON OUR BEST INHIBITOR. THIS INHIBITOR WILL BE EVALUATED: 1) AGAINST HUMAN NEUTROPHIL ELASTASE USING TRITIATED CALF LIGAMENT ELASTIN AS SUBSTRATE, 2) FOR CLEARANCE FROM HAMSTER LUNGS, AND 3) IN THE HAMSTER MODEL OF EMPHYSEMA USING HUMAN NEUTROPHIL ELASTASE. THESE OLIGOPEPTIDE INHIBITOR ASSAYS WILL BE CONDUCTED BY DRS. P. J. STONE AND E. C. LUCEY.

Principal Investigator:

Parish, Harlie A
Principal Investigator
9014541919

Business Contact:

1 r43 hl46621-01
Small Business Information at Submission:

Molecular Design International
P O Box 41777 Memphis, TN 38174

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