Nucleotide and oligonucleotide derivatives as enzyme and nucleic acid targeted irreversible inhibitors. Chemical aspects

Abstract

Reactive derivatives of nucleic acid components are the promising affinity reagents for specific modification of nucleic acids and nucleic acid-related proteins. Reactive ATP derivatives synthesized using the simple method described in the present chapter are potent specific inhibitors of various enzymes interacting with ATP. Reactive oligonucleotide derivatives bind to complementary nucleotide sequences in nucleic acids and modify them in the neighborhood of the binding area. Modification with these derivatives (complementary addressed modification) may become an efficient approach for specific arrest of certain cellular biopolymer biosynthesis and for site-directed mutagenesis. In this chapter, synthesis of alkylating oligonucleotide derivatives is described in detail and the results of their application for modification of nucleic acids in vitro are summarized. The results allow one to think about future biochemical and biomedical applications of complementary addressed modification.