Design and Chemical Synthesis of a Homogeneous Polymer-Modified Erythropoiesis Protein
Author:
Kochendoerfer Gerd G.1, Chen Shiah-Yun1, Mao Feng1, Cressman Sonya1, Traviglia Stacey1, Shao Haiyan1, Hunter Christie L.1, Low Donald W.1, Cagle E. Neil1, Carnevali Maia1, Gueriguian Vincent1, Keogh Peter J.1, Porter Heather1, Stratton Stephen M.1, Wiedeke M. Con1, Wilken Jill1, Tang Jie1, Levy Jay J.1, Miranda Les P.1, Crnogorac Milan M.1, Kalbag Suresh1, Botti Paolo1, Schindler-Horvat Janice1, Savatski Laura2, Adamson John W.2, Kung Ada1, Kent Stephen B. H.1, Bradburne James A.1
Affiliation:
1. Gryphon Therapeutics, 250 East Grand Avenue, Suite 90, South San Francisco, CA 94080, USA. 2. The Blood Research Institute, Blood Center of Southeastern Wisconsin, 8727 Watertown Plank Road, Milwaukee, WI 53226, USA.
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.
Publisher
American Association for the Advancement of Science (AAAS)
Subject
Multidisciplinary
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