Peptidyl carbamates as novel elastase inhibitors: structure-activity relationship studies
| Autor: | Kiyoshi Tsuji, Masayuki Kato, George A. Digenis, Bushra J. Agha, Abdul-Kareem Abdul-Raheem, William R. Banks |
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| Rok vydání: | 1993 |
| Předmět: |
Proteases
Stereochemistry Swine Molecular Sequence Data Biochemistry Serine Structure-Activity Relationship medicine Animals Humans Amino Acid Sequence Pancreatic elastase Pancreas chemistry.chemical_classification Chymotrypsin biology Pancreatic Elastase Elastase Trypsin Enzyme chemistry Enzyme inhibitor biology.protein Molecular Medicine Carbamates Leukocyte Elastase medicine.drug |
| Zdroj: | Journal of enzyme inhibition. 7(2) |
| ISSN: | 8755-5093 |
| Popis: | Twenty-six novel peptidyl carbamates and thiocarbamates were synthesized and evaluated as elastase inhibitors. Eighteen compounds inhibited porcine pancreatic elastase, whereas only eleven of the newly synthesized compounds inhibited human leukocyte elastase. Neither of the other serine dependent proteases, trypsin or chymotrypsin, were affected by any of the active inhibitors. Structure-activity relationship studies indicated that inhibition was dependent on P1 and P'1 substitution as well as on the presence of the carbamate functionality. Placement of an isostere of valine at P1 and a 1-(phenyl mercaptotetrazole at P'1 resulted in the most active human leukocyte elastase inhibitor within this series of compounds (Ki - 3.0 x 10(-7) M). |
| Databáze: | OpenAIRE |
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