Structure-activity relationships of omega-conotoxins at N-type voltage-sensitive calcium channels.
J Mol Recognit
; 13(2): 55-70, 2000.
Article
en En
| MEDLINE
| ID: mdl-10822250
Due to their selectivity towards voltage-sensitive calcium channels (VSCCs) omega-conotoxins are being exploited as a new class of therapeutics in pain management and may also have potential application in ischaemic brain injury. Here, the structure-activity relationships (SARs) of several omega-conotoxins including GVIA, MVIIA, CVID and MVIIC are explored. In addition, the three-dimensional structures of these omega-conotoxins and some structurally related peptides that form the cysteine knot are compared, and the effects of the solution environment on structure discussed. The diversity of binding and functional assays used to measure omega-conotoxin potencies at the N-type VSCC warranted a re-evaluation of the relationship between these assays. With one exception, [A22]-GVIA, this analysis revealed a linear correlation between functional (peripheral N-type VSCCs) and radioligand binding assays (central N-type VSCCs) for the omega-conotoxins and analogues that were tested over three studies. The binding and functional results of several studies are compared in an attempt to identify and distinguish those residues that are important in omega-conotoxin function as opposed to those that form part of the structural scaffold. Further to determining what omega-conotoxin residues are important for VSCC binding, the range of possible interactions between the ligand and channel are considered and the factors that influence the selectivity of MVIIA, GVIA and CVID towards N-type VSCCs examined.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Bloqueadores de los Canales de Calcio
/
Canales de Calcio Tipo N
/
Omega-Conotoxinas
Tipo de estudio:
Diagnostic_studies
/
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
J Mol Recognit
Asunto de la revista:
BIOLOGIA MOLECULAR
Año:
2000
Tipo del documento:
Article
País de afiliación:
Australia
Pais de publicación:
Reino Unido