Structure-function studies of two synthetic anti-vascular endothelial growth factor Fabs and comparison with the Avastin Fab.
作者： Germaine Fuh , Ping Wu , Wei-Ching Liang , Mark Ultsch , Chingwei V. Lee
关键词:
摘要: In the quest to discover new research tools and develop better agents in fight against cancer, two antibodies, G6 B20-4, were isolated from synthetic antibody phage libraries. Unlike AVASTIN™ antibody, a recently approved agent for treatment of patients with colorectal B20-4 bind block both human murine vascular endothelial growth factor (VEGF). Here we have analyzed compared binding epitopes on VEGF these three antibodies using alanine-scanning mutagenesis structural analyses. The recognized by are conserved between mouse VEGF, they match closely receptor structurally functionally. contrast, Avastin epitope overlaps minimally surface centers around residue that is not mouse. Our functional analyses elucidate cross-species reactivity all emphasize potential advantages generation display as resulting do depend sequence differences across species preferentially target natural protein-protein interaction surfaces.
rcsb.org参考文章(45)
Arinobu Tojo, Sachiko Yamaguchi, Masabumi Shibuya, Hitoshi Matsushime, Misako Sato, Toshio Ikeda, Akira Yamane, Nucleotide sequence and expression of a novel human receptor-type tyrosine kinase gene (flt) closely related to the fms family. Oncogene. ,vol. 5, pp. 519- 524 ,(1990)
Zbyszek Otwinowski, Wladek Minor, Processing of X-ray diffraction data collected in oscillation mode Methods in Enzymology. ,vol. 276, pp. 307- 326 ,(1997) , 10.1016/S0076-6879(97)76066-X
J. Marx, Angiogenesis. A boost for tumor starvation. Science. ,vol. 301, pp. 452- 454 ,(2003) , 10.1126/SCIENCE.301.5632.452
Bronislaw Pytowski, William O’Connor, Daniel J. Hicklin, Andrea Hooper, Yiwen Li, Karen King, Angel Santiago, Peter Bohlen, James Huber, Jay Overholser, Larry Witte, Marie Prewett, Antivascular Endothelial Growth Factor Receptor (Fetal Liver Kinase 1) Monoclonal Antibody Inhibits Tumor Angiogenesis and Growth of Several Mouse and Human Tumors Cancer Research. ,vol. 59, pp. 5209- 5218 ,(1999)
Leo C James, Pietro Roversi, Dan S Tawfik, Antibody Multispecificity Mediated by Conformational Diversity Science. ,vol. 299, pp. 1362- 1367 ,(2003) , 10.1126/SCIENCE.1079731
Christian Wiesmann, Germaine Fuh, Hans W. Christinger, Charles Eigenbrot, James A. Wells, Abraham M. de Vos, Crystal Structure at 1.7 Å Resolution of VEGF in Complex with Domain 2 of the Flt-1 Receptor Cell. ,vol. 91, pp. 695- 704 ,(1997) , 10.1016/S0092-8674(00)80456-0
K Jin Kim, Bing Li, Jane Winer, Mark Armanini, Nancy Gillett, Heidi S Phillips, Napoleone Ferrara, None, Inhibition of vascular endothelial growth factor-induced angiogenesis suppresses tumour growth in vivo Nature. ,vol. 362, pp. 841- 844 ,(1993) , 10.1038/362841A0
Yvonne Chen, Christian Wiesmann, Germaine Fuh, Bing Li, Hans W Christinger, Patrick McKay, Abraham M de Vos, Henry B Lowman, Selection and analysis of an optimized anti-VEGF antibody: crystal structure of an affinity-matured Fab in complex with antigen. Journal of Molecular Biology. ,vol. 293, pp. 865- 881 ,(1999) , 10.1006/JMBI.1999.3192
Christian Wiesmann, Hans W. Christinger, Andrea G. Cochran, Brian C. Cunningham, Wayne J. Fairbrother, Christopher J. Keenan, Gloria Meng, Abraham M. de Vos, Crystal structure of the complex between VEGF and a receptor-blocking peptide. Biochemistry. ,vol. 37, pp. 17765- 17772 ,(1998) , 10.1021/BI9819327
Chingwei V Lee, Wei-Ching Liang, Mark S Dennis, Charles Eigenbrot, Sachdev S Sidhu, Germaine Fuh, High-affinity Human Antibodies from Phage-displayed Synthetic Fab Libraries with a Single Framework Scaffold Journal of Molecular Biology. ,vol. 340, pp. 1073- 1093 ,(2004) , 10.1016/J.JMB.2004.05.051