Design and synthesis of type-III mimetics of ShK toxin
| Autor: | Jonathan B. Baell, Raymond S. Norton, Andrew John Harvey |
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| Rok vydání: | 2002 |
| Předmět: |
Models
Molecular Protein Conformation Peptidomimetic Stereochemistry In Vitro Techniques medicine.disease_cause Epitope Cnidarian Venoms Drug Discovery Potassium Channel Blockers medicine Animals Humans Physical and Theoretical Chemistry Binding Sites Molecular Structure Chemistry Toxin Molecular Mimicry Rational design Small molecule Computer Science Applications Structure and function Drug Design Computer-Aided Design Thermodynamics Pharmacophore Immunosuppressive Agents |
| Zdroj: | Journal of Computer-Aided Molecular Design. 16:245-262 |
| ISSN: | 1573-4951 0920-654X |
| Popis: | ShK toxin is a structurally defined, 35-residue polypeptide which blocks the voltage-gated Kv1.3 potassium channel in T-lymphocytes and has been identified as a possible immunosuppressant. Our interest lies in the rational design and synthesis of type-III mimetics of protein and polypeptide structure and function. ShK toxin is a challenging target for mimetic design as its binding epitope consists of relatively weakly binding residues, some of which are discontinuous. We discuss here our investigations into the design and synthesis of 1st generation, small molecule mimetics of ShK toxin and highlight any principles relevant to the generic design of type-III mimetics of continuous and discontinuous binding epitopes. We complement our approach with attempted pharmacophore-based database mining. |
| Databáze: | OpenAIRE |
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