Exploring the chiral space within the active site of α-thrombin with a constrained mimic of d -Phe-Pro-Arg — design, synthesis, inhibitory activity, and X-ray structure of an enzyme–inhibitor complex
| Autor: | Djorde Musil, Stephen Hanessian, Ingemar Nilsson, Lise-Lotte Olsson, Elise Balaux |
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| Rok vydání: | 2000 |
| Předmět: |
Models
Molecular Molecular model medicine.drug_class Stereochemistry Clinical Biochemistry Pharmaceutical Science Carboxamide Crystallography X-Ray Biochemistry Thrombin Drug Discovery medicine Enzyme Inhibitors Molecular Biology chemistry.chemical_classification Binding Sites Molecular Structure biology Chemistry Molecular Mimicry Organic Chemistry Active site Stereoisomerism Biological activity Trypsin Amino acid Enzyme inhibitor Molecular Probes biology.protein Molecular Medicine Oligopeptides medicine.drug |
| Zdroj: | Bioorganic & Medicinal Chemistry Letters. 10:243-247 |
| ISSN: | 0960-894X |
| Popis: | An indolizidinone motif with strategically placed substitutents was designed and synthesized as a constrained mimic of d -Phe-Pro-Arg. Low nanomolar inhibition of α-thrombin validates the design elements in this inhibitor which also exhibits a 20-fold selectivity for thrombin versus trypsin. An X-ray crystal structure of the inhibitor with α-thrombin shows the expected interactions with key amino acids within the active site and some notable changes in positions. |
| Databáze: | OpenAIRE |
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