Author/Authors :
Shiah-Yun Chen، نويسنده , , Sonya Cressman، نويسنده , , Feng Mao، نويسنده , , Haiyan Shao، نويسنده , , Donald W. Low، نويسنده , , Hal S. Beilan، نويسنده , , E. Neil Cagle، نويسنده , , Maia Carnevali، نويسنده , , Vincent Gueriguian، نويسنده , , Peter J. Keogh، نويسنده , , Heather Porter، نويسنده , , Stephen M. Stratton، نويسنده , , M. Con Wiedeke، نويسنده , , Laura Savatski، نويسنده , , John W. Adamson، نويسنده , , Carlos E. Bozzini، نويسنده ,
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.
