Design and synthesis of type-III mimetics of omega-conotoxin GVIA
Our interest lies in the rational design and synthesis of type-III mimetics of protein and polypeptide structure and function. Our approach involves interactive design of conformationally defined molecular scaffolds that project certain functional groups in a way that mimics the projection of import...
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| Veröffentlicht in: | Journal of computer-aided molecular design 2001-12, Vol.15 (12), p.1119-1136 |
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| container_end_page | 1136 |
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| container_issue | 12 |
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| container_title | Journal of computer-aided molecular design |
| container_volume | 15 |
| creator | Baell, J B Forsyth, S A Gable, R W Norton, R S Mulder, R J |
| description | Our interest lies in the rational design and synthesis of type-III mimetics of protein and polypeptide structure and function. Our approach involves interactive design of conformationally defined molecular scaffolds that project certain functional groups in a way that mimics the projection of important binding residues as determined in the parent structure. These design principles are discussed and applied to the structurally defined polypeptide, omega-conotoxin GVIA, which blocks voltage-gated, neuronal N-type calcium channels. These ion channels represent therapeutic targets for the development of new analgesics that can treat chronic pain. It is shown how a discontinuous, 3-residue pharmacophore of GVIA can be mimicked by different molecular scaffolds. It is illustrated how such 1st generation leads must necessarily be weak and that optimisability must therefore be built-in during the design process. |
| doi_str_mv | 10.1023/A:1015930031890 |
| format | Article |
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| language | eng |
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| source | MEDLINE; SpringerLink Journals |
| subjects | Analgesics - chemical synthesis Analgesics - chemistry Binding Sites Calcium Channel Blockers - chemical synthesis Calcium Channel Blockers - chemistry Calcium Channels, N-Type - chemistry Calcium Channels, N-Type - drug effects Crystallography, X-Ray Drug Design Humans In Vitro Techniques Magnetic Resonance Spectroscopy Models, Molecular Molecular Mimicry omega-Conotoxin GVIA - chemistry Protein Conformation |
| title | Design and synthesis of type-III mimetics of omega-conotoxin GVIA |
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