| Literature DB >> 15797221 |
Shiah-Yun Chen1, Sonya Cressman, Feng Mao, Haiyan Shao, Donald W Low, Hal S Beilan, E Neil Cagle, Maia Carnevali, Vincent Gueriguian, Peter J Keogh, Heather Porter, Stephen M Stratton, M Con Wiedeke, Laura Savatski, John W Adamson, Carlos E Bozzini, Ada Kung, Stephen B H Kent, James A Bradburne, Gerd G Kochendoerfer.
Abstract
Chemical synthesis in combination with precision polymer modification allows the systematic exploration of the effect of protein properties, such as charge and hydrodynamic radius, on potency using defined, homogeneous conjugates. A series of polymer-modified synthetic erythropoiesis proteins were constructed that had a polypeptide chain similar to the amino acid sequence of human erythropoietin but differed significantly in the number and type of attached polymers. The analogs differed in charge from +5 to -26 at neutral pH and varied in molecular weight from 30 to 54 kDa. All were active in an in vitro cell proliferation assay. However, in vivo potency was found to be strongly dependent on overall charge and size. The trends observed in this study may serve as starting points for the construction of more potent synthetic EPO analogs in the future.Entities:
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Year: 2005 PMID： 15797221 DOI： 10.1016/j.chembiol.2005.01.017
Source DB: PubMed Journal: Chem Biol ISSN： 1074-5521