Convenient synthesis of biopharmaceutic-Fc conjugates: Semi-synthesis and evaluation on the extension of their circulating plasma half-lives

Biopharmaceutics consisting of middle molecules, for example, peptide or nucleic-acid aptamers, have been attracting attention as promising molecular modalities in current drug discovery.

A major problem of such pharmaceutics for therapeutic applications is that the half-lives of their circulating plasma inside the body are too short. Ideally, a precise conjugation of the Fc fragment of human antibodies with pharmaceutics would extend the half-lives. Practically, the conjugation between the complicated molecules is still immature.

Now, Masumi Taki and colleagues at the University of Electro-Communications (UEC), and Ajinomoto Co. Inc. have established a facile and efficient semisynthesis method to obtain biopharmaceutics-Fc conjugates.

A combination of chemoenzymatic novel reaction (i.e., the NEXT-A reaction) followed by well-known click reaction yielded almost 100% conversion; and the N-terminal specific precise conjugation of the Fc fragment with different kinds of biopharmaceutics was unambiguously identified by several methods including deconvoluted mass spectrometry.

A Fc-conjugated (peptidic) pharmaceutic synthesized by this method led to a long-circulating plasma half-life inside mice while retaining its original biological activity.

The Fc-conjugation platform described can be applied many kinds of biopharmaceutics with different molecular modalities.

Reference

• Authors: Shigeo Hirasawa, Yoshiro Kitahara,Yoriko Okamatsu,Tomohiro Fujii, Akira Nakayama, Satoko Ueno, Chiori Ijichi, Fumie Futaki, Kunio Nakata, Masumi Taki.
• Title of original paper: Facile and Efficient Chemoenzymatic Semisynthesis of Fc-Fusion Compounds for Half-Life Extension of Pharmaceutical Components.
• Journal, volume, pages and year: Bioconjugate Chemistry, in press (2019).
• Digital Object Identifier (DOI): 10.1021/acs.bioconjchem.9b00235.
• Affiliations: Department of Engineering Science, Graduate School of Informatics and Engineering, the University of Electro-Communications (UEC).
• Department website: https://www.uec.ac.jp/eng/education/ie_graduate/s/index.html

• Author: Masumi Taki
• Affiliations: Associate Professor, Graduate School of Informatics and Engineering, School of Informatics and Engineering, The University of Electro-Communications, Tokyo.
• Department Website: http://tkl.pc.uec.ac.jp/