Hirulog peptides with scissile bond replacements resistant to thrombin cleavage
| Autor: | Bourdon Paul R, Hammond Charles E, John M. Maraganore, Toni Kline |
|---|---|
| Rok vydání: | 1991 |
| Předmět: |
Stereochemistry
Molecular Sequence Data Biophysics Hirudin Peptide Substrate analog Biochemistry chemistry.chemical_compound Scissile bond Structure-Activity Relationship Thrombin medicine Moiety Humans Amino Acid Sequence Anion binding Molecular Biology chemistry.chemical_classification Cell Biology Hirudins Amino acid Kinetics chemistry Indicators and Reagents Oligopeptides medicine.drug |
| Zdroj: | Biochemical and biophysical research communications. 177(3) |
| ISSN: | 0006-291X |
| Popis: | Using the natural protein hirudin as a model, a novel class of synthetic peptide inhibitors were recently designed. These inhibitors, ‘hirulogs’, retain the carboxy terminal Hir53–64 domain that interacts with the anion binding exosite of thrombin, connected via an oligoglycyl spacer unit to a catalytic site-directed moiety modeled on the sequence [D]Phe-Pro-Arg-X. The scissile Arg-X bond bond of substrate-like inhibitors has been modified to the proteolytic-resistant functions as β-homo amino acids Argψ[CH2CONH] X (2) and reduced bond analogues Argψ[CH2N]X (3). Both classes of compounds demonstrate inhibition of thrombin amidolytic activity, and this active-site inhibition is highly sensitive to the P1′ residue X. Thus these hirulog deriviatives are resistant to thrombin proteolysis while maintaining substrate-like interactions with the active center. Finally, hirulog derivatives with non-cleavable replacements of the scissile bond are found to be effective anticoagulant agents. |
| Databáze: | OpenAIRE |
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