STUDIES ON COOPERATIVE BINDING OF AN EXTENDED DISTAMYCIN-A ANALOG IN THE MINOR-GROOVE OF DNA BY NMR-SPECTROSCOPY

An analogue of the DNA minor groove binding antibiotic distamycin A, P 4(+), was found to bind in a 2:1 cooperative manner into the narrow gr oove of oligodeoxybibonucleotide d(CGTATATACG)(2) by 1D-NMR titration. The resulting 2:1 ligand-DNA complex was characterized by 2D NMR expe riments including NOESY, COSY, and TOCSY. Two molecules are oriented s ide by side opposite to each other; each has the N terminus to C termi nus direction parallel to the 5' to 3' direction of its adjacent DNA s trand. This study corroborates our previous CD and ethidium fluorometr y results and provides new support for the generality of the antiparal lel side by side binding motif first observed with distamycin A. (C) 1 996 Academic Press, Inc.