Linear scaffolds for multivalent targeting of melanocortin receptors.
Org Biomol Chem
; 13(47): 11507-17, 2015 Dec 21.
Article
en En
| MEDLINE
| ID: mdl-26461460
ABSTRACT
Molecules bearing one, two, three, or four copies of the tetrapeptide His-dPhe-Arg-Trp were attached to scaffolds based on ethylene glycol, glycerol, and d-mannitol by means of the copper-assisted azide-alkyne cyclization. The abilities of these compounds to block binding of a probe at the melanocortin 4 receptor were evaluated using a competitive binding assay. All of the multivalent molecules studied exhibited 30- to 40-fold higher apparent affinites when compared to a monovalent control. These results are consistent with divalent binding to receptor dimers. No evidence for tri- or tetravalent binding was obtained. Differences in the interligand spacing required for divalent binding, as opposed to tri- or tetravalent binding, may be responsible for these results.
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Oligopéptidos
/
Receptor de Melanocortina Tipo 4
Límite:
Humans
Idioma:
En
Revista:
Org Biomol Chem
Asunto de la revista:
BIOQUIMICA
/
QUIMICA
Año:
2015
Tipo del documento:
Article
País de afiliación:
Estados Unidos