Multivalency Increases the Binding Strength of RGD Peptidomimetic-Paclitaxel Conjugates to Integrin αV ß3.
Chemistry
; 23(58): 14410-14415, 2017 Oct 17.
Article
en En
| MEDLINE
| ID: mdl-28816404
ABSTRACT
This work reports the synthesis of three multimeric RGD peptidomimetic-paclitaxel conjugates featuring a number of αV ß3 integrin ligands ranging from 2 to 4. These constructs were assembled by conjugation of the integrin αV ß3 ligand cyclo[DKP-RGD]-CH2 NH2 with paclitaxel via a 2'-carbamate with a self-immolative spacer, the lysosomally cleavable Val-Ala dipeptide linker, a multimeric scaffold, a triazole linkage, and finally a PEG spacer. Two monomeric conjugates were also synthesized as reference compounds. Remarkably, the new multimeric conjugates showed a binding affinity for the purified integrin αV ß3 receptor that increased with the number of integrin ligands (reaching a minimum IC50 value of 1.2â
nm for the trimeric), thus demonstrating that multivalency is an effective strategy to strengthen the ligand-target interactions.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Oligopéptidos
/
Paclitaxel
/
Integrina alfaVbeta3
/
Peptidomiméticos
Idioma:
En
Revista:
Chemistry
Asunto de la revista:
QUIMICA
Año:
2017
Tipo del documento:
Article