Synthesis and Biological Characterization of Monomeric and Tetrameric RGD-Cryptophycin Conjugates.
Chemistry
; 26(12): 2602-2605, 2020 Feb 26.
Article
em En
| MEDLINE
| ID: mdl-31943410
ABSTRACT
The effective delivery of cytotoxic agents to tumor cells is a key challenge in anticancer therapy. Multivalent integrinspecific ligands are considered a promising tool to increase the binding affinity, selectivity, and internalization efficiency of small-molecule drug conjugates. Herein, we report the synthesis and biological evaluation of a multimeric conjugate containing the high-affinity integrin αv ß3 binding ligand RAFT-c(RGDfK)4 , a lysosomally cleavable Val-Cit linker, and cryptophycin-55 glycinate, a potent inhibitor of tubulin polymerization. In vitro cytotoxicity assays verified that the multimeric RGD-cryptophycin conjugate displays improved potency compared to the monomeric analogue in integrin αv ß3 overexpressing tumor cell lines, while significantly reduced activity was observed in the integrin-negative cell line.
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Base de dados:
MEDLINE
Assunto principal:
Peptídeos Cíclicos
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Portadores de Fármacos
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Depsipeptídeos
Limite:
Humans
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article