EXTENSIONS TO THE THEORY OF INTERCALATION

Though the nearest neighbor exclusion model provides a good semiquanti tative description of intercalation isotherms, it ignores the electros tatic interaction between cationic intercalators and DNA and underesti mates binding in the neighborhood of theta = 0.5 intercalators per bas e pair. In order to improve the analysis and interpretation of interca lative binding curves, we (1) propose and develop a model that permits restricted but partial occupation of nearest neighbor sites, (2) disc uss the advantages of using experimental variables for analysis rather than derived variables like theta/L for Scatchard plots, and (3) comb ine the lattice statistics of intercalation with the electrostatic fre e energy of intercalation as calculated by C. Bustamante and D. Stigte r [(1984) Biopolymers, Vol. 23, pp. 629-645] to generate an isotherm t hat contains both effects. The analysis of data via the latter theory provides a description of the intercalation not only as a function of ligand concentration but also as a function of ionic strength and thet a. The quantitative accuracy of the electrostatic theory can be checke d by the standard In K-I vs In C plots. [M. T. Record T. M. Lohman, an d P. de Haseth (1976) Journal of Molecular Biology, Vol. 107, pp. 145- 158], but appropriate data do not appear to be available at the presen t time. (C) 1996 John Wiley & Sons, Inc.