Site-specific conjugation of fibroblast growth factor 2 (FGF2) based on incorporation of alkyne-reactive unnatural amino acid

Bioorganic & Medicinal Chemistry
K W SwiderskaJ Otlewski

Abstract

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.

Citations

Aug 24, 2018·International Journal of Molecular Sciences·Julia ChudzianJacek Otlewski
Dec 24, 2018·Journal of Clinical Medicine·Natalia PorębskaŁukasz Opaliński
Jul 22, 2018·International Journal of Molecular Sciences·Karolina Weronika ŚwiderskaJacek Otlewski
Sep 22, 2021·Journal of Molecular Biology·Sanghee LeeMinseob Koh

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