Synthesis of PEGylated methotrexate conjugated with a novel CPP6, in sillico structural insights and activity in MCF-7 cells

• Tipo: Artigo em Revista Científica Internacional
• Data: 2019

Autores

Yang, V (Autor) Outra; Pedrosa, SS (Autor) Outra; Fernandes, R (Autor) Outra; Mauricio, AC (Autor) ICBAS; Koksch, B (Autor) Outra; Gartner, F (Autor) Outra; Amorim, I (Autor) Outra; Nuno Vale (Autor) ICBAS

Revista

Título: Journal of Molecular Structure

Vol. 1192

Páginas: 201-207

ISSN: 0022-2860

Editora: Elsevier

Indexação

ISI Web of Knowledge - 2 Citações

Scopus - 2 Citações

Outras Informações

ID Authenticus: P-00Q-M1S

DOI: 10.1016/j.molstruc.2019.04.118

Abstract (EN): Currently, most of the available chemotherapy has a narrow therapeutic window. This compromises the use of high-dose treatments in patients with advanced-stage cancers, who often need innovative strategies the most. Here, we present the conjugation of methotrexate with a novel cell-penetrating hexapeptide (CPP6), a GFLG enzymatically cleavable spacer, and a short-length polyethylene glycol. The modifications added to methotrexate were rationalized to improve the drug bioavailability, specificity, and cell entry. Our final conjugate, CPGM, was successfully synthesized in solid phase and in vitro cell viability assays have shown that this conjugated form of methotrexate retains cytostatic effect towards MCF-7 breast cancer cells. (C) 2019 Published by Elsevier B.V.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 7