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Updated: Jul 6, 2026

Synthesis of Protein Bioconjugates via Cysteine-maleimide Chemistry
Published on: July 20, 2016
Design and chemical synthesis of a homogeneous polymer-modified erythropoiesis protein
Gerd G Kochendoerfer1, Shiah-Yun Chen, Feng Mao
1Gryphon Therapeutics, 250 East Grand Avenue, Suite 90, South San Francisco, CA 94080, USA. Gkochendoerfer@gryphonRX.com
Abstract:
We report the design and total chemical synthesis of "synthetic erythropoiesis protein" (SEP), a 51-kilodalton protein-polymer construct consisting of a 166-amino-acid polypeptide chain and two covalently attached, branched, and monodisperse polymer moieties that are negatively charged. The ability to control the chemistry allowed us to synthesize a macromolecule of precisely defined covalent structure. SEP was homogeneous as shown by high-resolution analytical techniques, with a mass of 50,825 +/-10 daltons by electrospray mass spectrometry, and with a pI of 5.0. In cell and animal assays for erythropoiesis, SEP displayed potent biological activity and had significantly prolonged duration of action in vivo. These chemical methods are a powerful tool in the rational design of protein constructs with potential therapeutic applications.
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