Base pairs with 5-(hydroxymethyl)-2′-deoxyuridine (HMdU) opposite either adenine or guanine in a seven-base oligonucleotide duplex have been studied by NMR spectroscopy. When paired with A, the HMdU-A base pair is in Watson-Crick geometry. The hydroxymethyl group maintains a fixed orientation in which the oxygen is on the 5′ side of the base. The energy-minimized structure indicates the presence of a hydrogen bond between the hydroxymethyl group and the N7 of the 5′ guanine residue. When paired with guanine, HMdU-G is in a wobble configuration at low pH. The hydroxymethyl group is on the 3′ side of the base, positioned to form an intramolecular hydrogen bond with its own 04 carbonyl. With increasing pH, HMdU-G is observed to ionize with an apparent pK value of 9.7. The high-pH structure is in a Watson-Crick configuration, with the HMdU residue in a position similar to that observed for HMdU-A. It is proposed that interresidue hydrogen bonding of the HMdU residue may stabilize aberrant base-pair configurations.
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