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Eur J Med Chem ; 85: 139-46, 2014 Oct 06.
Artículo en Inglés | MEDLINE | ID: mdl-25084142

RESUMEN

Bi-nuclear amino acid platforms loaded with various drugs for conjugation to a peptide carrier were synthesized using simple and convenient orthogonally protective solid-phase organic synthesis (SPOS). Each arm of the platform carries a different anticancer agent linked through the same or different functional group, providing discrete chemo- and bio-release profiles for each drug, and also enabling "switch off/switch on" regulation of drug cytotoxicity by conjugation to the platform and to a cell targeting peptide. The versatility of this approach enables efficient production of drug-loaded platforms and determination of favorable drug combinations/modes of linkage for subsequent conjugation to a carrier moiety for targeted cancer cell therapy. The results presented here potentiate the application of amino acid platforms for targeted drug delivery (TDD).


Asunto(s)
Antineoplásicos/química , Antineoplásicos/farmacología , Portadores de Fármacos/química , Aminoácidos/química , Animales , Antineoplásicos/toxicidad , Línea Celular Tumoral , Portadores de Fármacos/síntesis química , Portadores de Fármacos/metabolismo , Estabilidad de Medicamentos , Humanos , Hígado/metabolismo , Ratones
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