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

• Type: Article in International Scientific Journal
• Date: 2019

Authors

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

Journal

Title: Journal of Molecular Structure

Vol. 1192

Pages: 201-207

ISSN: 0022-2860

Publisher: Elsevier

Indexing

ISI Web of Knowledge - 2 Citations

Scopus - 2 Citations

Other information

Authenticus ID: 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.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 7