Synthetic peptide inhibitors of complement serine proteases—III. Significant increase in inhibitor potency provides further support for the functional equivalence hypothesis
| Autor: | Janet C. Mayden, Charles Steven Schasteen, Rory F. Finn, George Irvin Glover, Sharon A. McLafferty, Lea D. Bullock, R. Paul Levine |
|---|---|
| Rok vydání: | 1991 |
| Předmět: |
Proteases
alpha 1-Antichymotrypsin Antithrombin III Molecular Sequence Data Immunology In Vitro Techniques Serpin Complement Hemolytic Activity Assay Structure-Activity Relationship Classical complement pathway medicine Humans Amino Acid Sequence Complement Activation Molecular Biology Serpins Serine protease biology Protease binding Antithrombin Complement system carbohydrates (lipids) Biochemistry alpha 1-Antitrypsin biology.protein Alternative complement pathway Peptides medicine.drug |
| Zdroj: | Molecular Immunology. 28:17-26 |
| ISSN: | 0161-5890 |
| Popis: | Synthetic peptides based on functionally equivalent (as defined by similar patterns of chemically equivalent amino acids) serine protease inhibitor (serpin) C-terminal sequences inhibit both classical and alternative pathways of complement activation. Inhibition was also found with hybrid peptides consisting of the cleavage site of one serpin (antithrombin III, alpha-1-antitrypsin, or antichymotrypsin) attached to the short and long functionally equivalent protease binding cores of the other two serpins. A hybrid peptide composed of the sequence at the site of cleavage of C4 by C1s attached to the long binding core of antithrombin III was selective in inhibiting the classical pathway with no effect on the alternative pathway at a concn of 10 microM. Extension of the functional equivalence hypothesis has produced inhibitors of complement activation named generic and generic +, whose sequences differ by 77% or 87%, respectively, from those of all three serpin sequences. A hybrid peptide composed of the antithrombin III cleavage site attached to the generic peptide is an inhibitor of complement activation at 500 nM, the most potent inhibitor found in this study. |
| Databáze: | OpenAIRE |
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