Design and Chemical Synthesis of a Homogeneous Polymer-Modified Erythropoiesis Protein

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Science  07 Feb 2003:
Vol. 299, Issue 5608, pp. 884-887
DOI: 10.1126/science.1079085

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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.

  • * To whom correspondence should be addressed. E-mail: Gkochendoerfer{at}

  • Present address: Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of British Columbia, 2146 Health Sciences Mall, Vancouver, BC V6T 1Z3, Canada.

  • Present address: Diosynth RTP, Inc., 3000 Weston Parkway, Cary, NC 27513, USA.

  • § Present address: Applied Biosystems, 850 Lincoln Centre Drive, Foster City, CA 94404, USA.

  • || Present address: Celera Genomics, 180 Kimball Way, South San Francisco, CA 94080, USA.

  • Present address: Midwest Biotech, 12690 Ford Drive, Fishers, IN 46038–1151, USA.

  • # Present address: GeneProt Inc., 2 Pré-de-la-Fontaine, 1217 Meyrin/Geneva, Switzerland.

  • ** Present address: Departments of Biochemistry & Molecular Biology, and The University of Chicago, Chicago, IL 60637, USA.

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