Synthetic Erythropoietic Proteins: Tuning Biological Performance by Site-Specific Polymer Attachment

作者: Shiah-Yun Chen , Sonya Cressman , Feng Mao , Haiyan Shao , Donald W. Low

DOI: 10.1016/J.CHEMBIOL.2005.01.017

关键词:

摘要: Chemical synthesis in combination with precision polymer modification allows the systematic exploration of effect protein properties, such as charge and hydrodynamic radius, on potency using defined, homogeneous conjugates. A series polymer-modified synthetic erythropoiesis proteins were constructed that had a polypeptide chain similar to amino acid sequence human erythropoietin but differed significantly number type attached polymers. The analogs from +5 -26 at neutral pH varied molecular weight 30 54 kDa. All active an vitro cell proliferation assay. However, vivo was found be strongly dependent overall size. trends observed this study may serve starting points for construction more potent EPO future.

参考文章(41)
N Komatsu, M Yamamoto, H Fujita, A Miwa, K Hatake, T Endo, H Okano, T Katsube, Y Fukumaki, S Sassa, Establishment and characterization of an erythropoietin-dependent subline, UT-7/Epo, derived from human leukemia cell line. UT-7 Blood. ,vol. 82, pp. 456- 464 ,(1993) , 10.1182/BLOOD.V82.2.456.BLOODJOURNAL822456
M J Knauf, D P Bell, P Hirtzer, Z P Luo, J D Young, N V Katre, Relationship of effective molecular size to systemic clearance in rats of recombinant interleukin-2 chemically modified with water-soluble polymers. Journal of Biological Chemistry. ,vol. 263, pp. 15064- 15070 ,(1988) , 10.1016/S0021-9258(18)68146-3
Kenneth Jacobs, Charles Shoemaker, Richard Rudersdorf, Suzanne D. Neill, Randal J. Kaufman, Allan Mufson, Jasbir Seehra, Simon S. Jones, Rodney Hewick, Edward F. Fritsch, Makoto Kawakita, Tomoe Shimizu, Takaji Miyake, Isolation and characterization of genomic and cDNA clones of human erythropoietin Nature. ,vol. 313, pp. 806- 810 ,(1985) , 10.1038/313806A0
Ryan J. Darling, Uma Kuchibhotla, Wolfgang Glaesner, Radmila Micanovic, Derrick R. Witcher, John M. Beals, Glycosylation of erythropoietin affects receptor binding kinetics: role of electrostatic interactions. Biochemistry. ,vol. 41, pp. 14524- 14531 ,(2002) , 10.1021/BI0265022
Keith Rose, Facile synthesis of homogeneous artificial proteins Journal of the American Chemical Society. ,vol. 116, pp. 30- 33 ,(1994) , 10.1021/JA00080A004
Gerd G. Kochendoerfer, Janette M. Tack, Sonya Cressman, Total chemical synthesis of a 27 kDa TASP protein derived from the MscL ion channel of M. tuberculosis by ketoxime-forming ligation Bioconjugate Chemistry. ,vol. 13, pp. 474- 480 ,(2002) , 10.1021/BC010128L
Lynne E. Canne, Adrian R. Ferre- D'Amare, Stephen K. Burley, Stephen B. H. Kent, TOTAL CHEMICAL SYNTHESIS OF A UNIQUE TRANSCRIPTION FACTOR-RELATED PROTEIN : CMYC-MAX Journal of the American Chemical Society. ,vol. 117, pp. 2998- 3007 ,(1995) , 10.1021/JA00116A005
Jun Shao, James P. Tam, Unprotected Peptides as Building Blocks for the Synthesis of Peptide Dendrimers with Oxime, Hydrazone, and Thiazolidine Linkages Journal of the American Chemical Society. ,vol. 117, pp. 3893- 3899 ,(1995) , 10.1021/JA00119A001