Sequence-specific DNA binding by short peptides

Abstract

Publisher Summary This chapter discusses the recent development in designing novel sequence-specific DNA-binding peptides by using a combination of synthetic organic, biochemical, and molecular biological approaches to study the principles of molecular recognition associated with protein–DNA interactions. Understanding recognition from the chemical and physical standpoints requires a better understanding of the energetic differences between the specific and nonspecific protein–DNA interactions. The chapter describes model systems, which addresses the issues of protein–protein and protein–DNA recognition in far greater detail than is possible with the native protein systems. These peptide dimers apply a steric constraint on the two DNA contact regions of the dimeric peptides because the formation of well-ordered dimer determines the relative orientation of each monomer. Another role for the protein dimerization domain is to modulate the cooperativity of DNA binding by noncovalent protein–protein interactions. The protein–protein interaction plays an essential role in both enhancing the selectivity of specific DNA binding and increasing the sensitivity of equilibrium binding to changes in protein concentration. The chapter also presents the model systems with noncovalent dimerization domains.