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From catalytic asymmetric synthesis to the transcriptional regulation of genes: In vivo and in vitro evolution of proteins

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Barbas III, C. F., Rader, C., Segal, D. J., List, B., & Turner, J. M. (2001). From catalytic asymmetric synthesis to the transcriptional regulation of genes: In vivo and in vitro evolution of proteins. In F. H. Arnold (Ed.), Advances in Protein Chemistry, Vol. 55 (pp. 317-366). New York: Academic Press.


Cite as: http://hdl.handle.net/11858/00-001M-0000-0019-D60E-A
Abstract
This chapter focuses on the laboratory use of molecular evolution and discusses the selection to shape the novel proteins of defined function. The chapter discusses the types of function that involve the antibody/antigen interactions of the classical type (simple binding), the nonclassical type (catalysis), and the molecular recognition of long DNA addresses in complex genomes. The ability to manipulate the expression of specific endogenous genes would have wide-ranging applications in medicine and experimental and applied biology. In the therapy of cancer, for example, oncogenes, angiogenic factors, metastatic factors, and drug resistance genes are all potential targets for down regulation, while tumor suppressors, immunostimulants, and apoptotic factors could be targets for specific up regulation. Transcription factors are modular proteins consisting typically of a DNA-binding domain that provides for localization of the protein to a specific DNA address, and an effector domain that directs the type of activity to take place at the site. The wide range of effector activities available provide significant advantages over other proposed technologies.