Cooperative triple-helix formation via a minor groove dimerization domain

Abstract

Cooperative interactions between DNA-binding proteins are critical to the regulation of gene expression. When cooperative interactions occur between two oligonucleotides bound at neighboring sites on double-helical DNA, the specific binding of each oligonucleotide is enhanced. Pyrimidine oligodeoxyribonucleotides 11 bases in length bind cooperatively to abutting sites on double-helical DNA by triple-helix formation. Cooperative interactions up to 2.3 kcal mol^(-1) were obtained by addition of dimerization domains to oligonucleotides such as those capable of forming a short Watson−Crick helix. The designed polyamide ImPyPy binds sequence specifically to the minor groove of DNA at 5'-(T,A)G(T,A)C(T,A)-3' sites as a cooperative side-by-side antiparallel homodimer. We report here that a pyrrole−imidazole polyamide oligonucleotide can bind cooperatively to a double-stranded DNA template via a sequence specific polyamide dimerization domain.

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