Selective Binding of Synthetic Polypeptides to DNA of Varying Composition and Sequence: Effect of Minor Groove Binding Drugs

Abstract

Repetitive basic polypeptides containing lysine or arginine as every third amino acid were shown to cause DNA condensation at physiological salt concentration connected with selective DNA binding with respect to DNA composition and sequence. This selectivity is very similar to that existing in the case of histone H1 and other basic proteins and does not depend on polypeptide chain conformation. The effect of the minor groove binding drugs netropsin and distamycin was tested to elucidate the origin of the binding selectivity. The results suggest that the binding preferences are due to the variations in the conformation in various types of B-DNA that depend on DNA composition and sequence. The most important factor affecting the selectivity is probably the value of the negative electrostatic potential in the minor groove.