期刊
BIOORGANIC & MEDICINAL CHEMISTRY
卷 25, 期 14, 页码 3685-3693出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmc.2017.05.003
关键词
Unnatural amino acid incorporation; CuAAC reaction; Fibroblast growth factor 2 (FGF2); Cytotoxic drug conjugate
资金
- Polish-Norwegian Research Programme [Pol-Nor/197969/50/2013]
Recent advances in site-specific protein modification include the increasingly popular incorporation of unnatural amino acid(s) using amber codon, a method developed by Schultz and coworkers. In this study, we employ this technique to introduce propargyllysine (PrK) in human fibroblast growth factor 2 (FGF2). Owing to an alkyne moiety in its side chain, PrK is compatible with Cu(I)-catalyzed azide-alkyne 1,3-dipolar cycloaddition (CuAAC). We successfully tested CuAAC-mediated conjugation of FGF2 with two compounds - a fluorophore carboxyrhodamine 110 or a cytotoxic drug monomethyl auristatin E (MMAE). In the case of the MMAE conjugate we improved the initial poor conjugation yield to achieve nearly 100% efficiency after extensive optimization. The detergent-based optimization approach may help overcome problems with the CuAAC reaction yield for protein modification with hydrophobic compounds, such as MMAE. (C) 2017 Published by Elsevier Ltd.
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