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Design and Chemical Synthesis of a Homogeneous Polymer-Modified Erythropoiesis Protein
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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Metadata
- Authors
- Kochendoerfer, G. G., Chen, S.-Y., Mao, F., Cressman, S., Traviglia, S., Shao, H., Hunter, C. L., Low, D. W., Cagle, E. N., Carnevali, M., Gueriguian, V., Keogh, P. J., Porter, H., Stratton, S. M., Wiedeke, M. C., Wilken, J., Tang, J., Levy, J. J., Miranda, L. P., Crnogorac, M. M., Kalbag, S., Botti, P., Schindler-Horvat, J., Savatski, L., Adamson, J. W., Kung, A., Kent, S. B. H., & Bradburne, J. A.
- Venue
- Science
- Published
- 2003-02-07
- Volume
- 299
- Issue
- 5608
- Pages
- 884-887
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2102893844
- Cited by
- 312
- References
- 0
- FWCI
- 11.35
- Type
- journal article
- Language
- en
- Open access
- closed
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- The paper
- Kochendoerfer, G. G., Chen, S.-Y., Mao, F., Cressman, S., Traviglia, S., Shao, H., Hunter, C. L., Low, D. W., Cagle, E. N., Carnevali, M., Gueriguian, V., Keogh, P. J., Porter, H., Stratton, S. M., Wiedeke, M. C., Wilken, J., Tang, J., Levy, J. J., Miranda, L. P., . . . Bradburne, J. A. (2003). Design and Chemical Synthesis of a Homogeneous Polymer-Modified Erythropoiesis Protein. Science. https://doi.org/10.1126/science.1079085
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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