Development of chloride channel modulators.
Kidney Int
; 48(4): 985-93, 1995 Oct.
Article
em En
| MEDLINE
| ID: mdl-8569108
ABSTRACT
Chloride channels are ubiquitously distributed, biophysically varied and functionally diverse. Despite the known contribution of chloride channels to the physiology of various cell types and the pathology of several diseases, high affinity ligands are not available to study these channels. Here we report the iterative and integrated use of ion channel kinetic analysis and computational chemical methods in the development of high affinity blockers of the outwardly rectifying chloride channel (ORCC). Kinetic analysis, with emphasis on estimation of the block time constant as determined from critical closed time plots, was used to guide the synthesis of new disulfonic stilbene derivatives. Computational chemical methods were used to deduce the important features of the disulfonic stilbene molecule necessary for potent blockade of ORCC and ultimately led to the discovery of the calixarenes. Para-sulfonated calixarenes were found to be potent blockers of ORCC with subnanomolar inhibition constants and exceptionally long block times.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Canais de Cloreto
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Kidney Int
Ano de publicação:
1995
Tipo de documento:
Article
País de afiliação:
Estados Unidos