| Abstract
| - Cationic porphyrins such as meso-tetrakis(4-(N-methylpyridiumyl))porphyrin, or H2T4, are remarkably versatileDNA binding agents of interest for potential therapeutic applications. This study focuses on the influence theDNA bases have in determining the mode of uptake and the relative binding affinity. For convenience thehost is usually a DNA hairpin formed spontaneously by a 16-mer with the sequence 5‘-GAXYACTTTTGTY‘X‘TC-3‘, where X and Y designate varying nucleotides with complements X‘ and Y‘. Results fromabsorbance, emission, and CD spectroscopies lead to several conclusions. Among these is the recognitionthat the base composition, far more than the base sequence, dictates the mode of binding. Thus, any run ofDNA containing at least 50% G⋮C base pairs supports intercalative binding simply because a robust hydrogen-bonding framework (1) stabilizes the intercalated adduct, and (2) inhibits distortions that favor external binding.Another striking finding is that there is hardly any difference in binding constant for a hairpin that supportsintercalation as compared with one that supports external binding, despite the host of factors that go into theenergy balance. Finally, in and of itself, the steric bulk of the thymine methyl group does not prevent H2T4from intercalating in AT-rich regions of DNA because uridine-for-thymine base replacement has no effecton adduct formation.
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