Base−Base Recognition of Nonionic Dinucleotide Analogues in an Apolar Environment Studied by Low-Temperature NMR Spectroscopy

摘要

Abstract: Two self-complementary dinucleotide analogues TSiA and ASiT with a nonionic diisopropylsilyl-nmodified backbone were synthesized, and their association in a nonaqueous aprotic environment was studiednby NMR spectroscopy. Using a CDClF2/CDF3 solvent mixture, measurements at temperatures as low asn113 K allowed the observation and structural characterization of individual complexes in the slow exchangenregime. The ASiT analogue associates to exclusively form a dinucleotide antiparallel duplex with regularnWatson Crick base pairing, but both A and T nucleosides exhibit a predominant C3′-endo sugar puckernreminiscent of an A-type conformation. In contrast to ASiT, the TSiA dinucleotide is found to exhibit significantnvariability and flexibility. Thus, different secondary structures with weaker hydrogen bonds for all TSiAnstructures are observed at low temperatures. Although a B-like Watson Crick antiparallel dinucleotidenduplex with a preferred C2′-endo sugar pucker largely predominates at temperatures above 153 K, twonadditional species, namely a dinucleotide Hoogsteen duplex with a syn glycosidic torsion angle of thenadenosine nucleoside and a presumably intramolecularly folded structure, are increasingly populated uponnfurther cooling. By adding typical DNA intercalators like anthracene or benz[c]acridine derivatives to thenASiT dinucleotide duplex in the aprotic solvent environment, no binding of the polycyclic aromatic moleculesncan be detected even at lower temperatures. Obviously, van der Waals and stacking interactions areninsufficient to compensate for the other unfavorable contributions to the overall free energy of binding, andnonly in the presence of additional hydrophobic effects in an aqueous environment does binding occur.