Enhanced ligand affinity for receptors in which components of the binding site are independently mobile.
Chem Biol
; 12(1): 89-97, 2005 Jan.
Article
em En
| MEDLINE
| ID: mdl-15664518
ABSTRACT
Using calmodulin antagonism as a model, it is demonstrated that, under circumstances in which binding sites are motionally independent, it is possible to create bifunctional ligands that bind with significant affinity enhancement over their monofunctional counterparts. Suitable head groups were identified by using a semiquantitative screen of monofunctional tryptophan analogs. Two bifunctional ligands, which contained two copies of the highest-affinity head group tethered by rigid linkers, were synthesized. The bifunctional ligands bound to calmodulin with a stoichiometry of 11 and with an affinity enhancement over their monofunctional counterparts; the latter bound with a stoichiometry of 21 ligandprotein. A lower limit to the effective concentrations of the domains of calmodulin relative to each other (0.2-2 mM) was determined. A comparable effective concentration was achieved for bifunctional ligands based on higher-affinity naphthalene sulphonamide derivatives.
Buscar no Google
Base de dados:
MEDLINE
Assunto principal:
Triptofano
/
Calmodulina
/
Receptores de Detecção de Cálcio
/
Movimento
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Chem Biol
Assunto da revista:
BIOLOGIA
/
BIOQUIMICA
/
QUIMICA
Ano de publicação:
2005
Tipo de documento:
Article
País de afiliação:
Reino Unido