Sequence Specific Recognition of Double Helical DNA. A Synthetic Approach

Abstract

The design of synthetic sequence-specific DNA-binding molecules has advanced in recent years due, in part, to analytical techniques such as foot-printing and affinity cleaving which allow rapid and precise analyses of hundreds of potential DNA-binding sites to nucleotide resolution on sequencing gels (Dervan 1986). During the past 10 years our group has focused on the construction of molecules that bind in the minor and major groove of DNA with incrementally increasing sequence specificity as a first step toward defining the chemical principles for creating specificity at the 15-base pair level (Dervan 1986). Recent progress illustrates how the tools of chemical synthesis in combination with nucleic acid techniques can be used to solve this problem. This may lead to new research tools useful in molecular biology, diagnosis of disease states at the level of DNA, and novel chemotherapeutic strategies such as artificial repressors for inactivation of these genes. The purpose of this chapter is not a comprehensive survey of the literature but rather a brief report of recent progress from our group using an experimental approach to the design of sequence-specific DNA-binding molecules.

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