Exploring new near-infrared fluorescent disulfide-based cyclic RGD peptide analogs for potential integrin-targeted optical imaging.
Bioorg Med Chem Lett
; 21(7): 2116-20, 2011 Apr 01.
Article
em En
| MEDLINE
| ID: mdl-21349709
ABSTRACT
We synthesized disulfide-based cyclic RGD pentapeptides bearing a near-infrared fluorescent dye (cypate), represented by cypate-c(CRGDC) (1) for integrin-targeted optical imaging. These compounds were compared with the traditional lactam-based cyclic RGD counterpart, cypate-c(RGDfK) (2). Molecular modeling suggests that the binding affinity of 2 to integrin α(v)ß(3) is an order of magnitude higher than that of 1. This was confirmed experimentally, which further showed that substitution of Gly with Pro, Val and Tyr in 1 remarkably hampered the α(v)ß(3) binding. Interestingly, cell microscopy with A549 cells showed that 1 exhibited higher cellular staining than 2. These results indicate that factors other than receptor binding affinity to α(v)ß(3) dimeric proteins mediate cellular uptake. Consequently, 1 and its analogs may serve as valuable molecular probes for investigating the selectivity and specificity of integrin targeting by optical imaging.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Oligopeptídeos
/
Integrinas
/
Dissulfetos
/
Corantes Fluorescentes
Tipo de estudo:
Prognostic_studies
Idioma:
En
Ano de publicação:
2011
Tipo de documento:
Article