Structure-function relationships of hirulog peptide interactions with thrombin
| Autor: | Betty H. Chao, Bourdon Paul R, John M. Maraganore, Jablonski Jo-Ann M |
|---|---|
| Rok vydání: | 1991 |
| Předmět: |
Hirudin
Anions Inhibitor Peptidomimetic Stereochemistry Molecular Sequence Data Biophysics Peptide Hirulog Fibrinogen Biochemistry Binding Competitive Structure-Activity Relationship Thrombin Structural Biology Genetics medicine Amino Acid Sequence Molecular Biology chemistry.chemical_classification Binding Sites biology Chemistry Sulfates Cell Biology Hirudins Enzyme Enzyme inhibitor biology.protein Tyrosine medicine.drug Discovery and development of direct thrombin inhibitors Iodine |
| Zdroj: | FEBS letters. 294(3) |
| ISSN: | 0014-5793 |
| Popis: | Using hirudin as a model, a novel class of bivalent thrombin inhibitors has been designed and characterized (Maraganore et al. (1990) Biochemistry 29, 7095–7101). These peptides, designated ‘hirulogs’, interact with both thrombin's catalytic center and its anion-binding exosite for fibrinogen recognition. In order to investigate structure-activity relationships in hirulog peptides, a number of peptide and peptidomimetic derivatives with alterations in catalytic-site binding and anion-binding exosite binding moieties were prepared. Replacements or modifications in the catalytic site and exosite binding moieties were achieved with the consequences of maintaining or improving antithrombin activity. In addition to showing improved affinity for thrombin, some derivatives with K1's in the sub-nanomolar range showed increased anticoagulant activities. These findings highlight the versatility of hirulog peptides in their bivalent interactions with thrombin. |
| Databáze: | OpenAIRE |
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