Targeted antitumor prodrug therapy using CNGRC-yCD fusion protein in combination with 5-fluorocytosine

Journal of Biomedical Science
Jia-Je LiCheng Allen Chang

Abstract

The enzyme-prodrug system is considered a promising tool for tumor treatment when conjugated with a targeting molecule. The asparagine-glycine-arginine (NGR) motif is a developing and interesting targeting peptide that could specifically bind to aminopeptidase N (APN), which is an NGR receptor expressed on the cell membrane of angiogenic endothelial cells and a number of tumor cells within the tumor tissues. The objective of this study was to develop a novel targeted enzyme-prodrug system using 5-fluorocytosine (5-FC) and an NGR-containing peptide fused with yeast cytosine deaminase (yCD), i.e. CNGRC-yCD fusion protein, to target APN-expressing cells within the tumor tissues and to convert 5-FC into 5-fluorouracil (5-FU) to kill tumors. Both yCD and CNGRC-yCD proteins were cloned into the pET28a vector and expressed by an Escherichia coli host. Both yCD and CNGRC-yCD proteins were purified and the yields were approximately 20 mg/L with over 95 % purity. The binding assay demonstrated that the CNGRC-yCD fusion protein had specific binding affinity toward purified APN recombinant protein and high-APN-expressing cells, including human endothelial cells (HUVECs) and various types of human tumor cell lines, but not low-APN-expressin...Continue Reading

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Citations

Jun 21, 2017·Journal of Materials Chemistry. B, Materials for Biology and Medicine·Maurizio RoveriPaola Luciani
Apr 3, 2020·Cell Biology and Toxicology·Samira ValiyariSaeid Bouzari

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Methods Mentioned

BETA
phage display
transfection
protein assay
PCR
gel filtration
electrophoresis
enzyme-linked immunosorbent assay
ELISA
flow cytometry

Software Mentioned

GraphPad Prism

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