Biochemistry Influence of the Furanose on the Conformation of Adenine Dinucleoside Monophosphates in Solution4dR

The influence of the 2′-hydroxyl group on nucleic acid conformation has been investigated by studying the solution conformations of six adenine dinucleoside monophosphates, rAprA, dApdA, rApdA, dAprA, rA5′p5′rA, and dA5′P5′dA, concurrently by the methods of ultraviolet (uv) hypochromicity, circular dichroism (CD), and proton magnetic resonance (pmr) spectroscopy. The pmr spectral assignments of rApdA, dAprA, and dA5′p5′dA were made by the use of specifically deuterated dimers, dAp-8-D-rA and 8D-rApdA, deuterium-exchange studies, and molecular models; while pmr spectra of other dimers have been previously assigned. The conformational models of these dimers were constructed on the basis of these studies and were shown to be right-handed stacks with both nucleosidyl units in the anti conformation. The order of base-base stacking determined by both hypochromicity and pmr dimerization shifts is rA5~ P5′rA dA5′-p5′dA > dApdA dAprA > rAprA rApdA. The CD spectra of the six dimers are qualitatively similar, although the amplitude in [0] follows the order rA5-p5′rA > dA5′p5′dA; rAprA > dApdA dAprA > rApdA, which i different from the order of stacking found by pmr and uv measurements. The CD data may be more sensitive to the variances in the mode of the base-base orientation in different stacks, or in the proportion between the right-handed conformers and the left-handed conformers in solution. The results from this investigation together with those from previous studies indicate that the influence of the 2′-OH group of the ribose on the conformation of the ribose-containing dimers is exerted through the steric hindrance of this group and not through its hydrogen-bonding properties. Upon stacking, the ribose of the 3′-residue is compressed by the furanose of the adjacent 5 ′ residue (possibly by the base of the 5 ′ residue as well). This steric interference between the 3′-furanose group and the immediately following 5 ′ residue prevents an extensive overlap of the adenines in a parallel fashion. Such an interference is absent in the dimers containing a deoxyribosyl 3′ residue, such as dApdA and dAprA.