Nucleic Acids Research: VOLUME 39 ISSUE 1 2011

Experiments are described that measure DNA dissociation kinetics and thermal denaturation temperatures for a series of actinomycin analogs containing, in the 3' amino acid position, pipecolic acid, proline or azetidine-2-carboxyiic acid. Also included are studies on actinomycin Co. Analysis of the temperature dependence of the slowest rate constant for DNA dissociation shows that both tbe enthalpy and entropy of activation increase as the ring size of the 3' amino acid decreases from six to five to four. All compounds increase the DNA melting temperature to the same extent except for tbe analog containing pipecolic acid, which shows a smaller effect. These results are discussed in terms of a possible role for conformational changes in the actinomycin pentapeptide lactone rings in determining the slow DNA dissociations rates for this class of intercalators. It is suggested that cis-trans isomerization of proline may be important in this regard.