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An Unnatural Hydrophobic Base Pair with Shape Complementarity between Pyrrole-2-carbaldehyde and 9-Methylimidazo[(4,5)-b]pyridine

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journal contribution
posted on 11.04.2003, 00:00 by Tsuneo Mitsui, Aya Kitamura, Michiko Kimoto, Taiko To, Akira Sato, Ichiro Hirao, Shigeyuki Yokoyama
An unnatural hydrophobic base, pyrrole-2-carbaldehyde (denoted as Pa), was developed as a specific pairing partner of 9-methylimidazo[(4,5)-b]pyridine (Q). The Q base is known to pair with 2,4-difluorotoluene (F) as an isostere of the AT pair, and F also pairs with A efficiently in replication. In contrast, the QPa pair showed specific selectivity in replication, and the five-membered-ring base Pa paired efficiently with Q but paired poorly with A. In addition, the interaction of Pa with DNA polymerases was superior, in comparison to that of F. The aldehyde group of Pa was recognized well by the Klenow fragment of Escherichia coli DNA polymerase I and the reverse transcriptase of Avian myeloblastosis virus. The structural features of the QPa pair in a DNA duplex were analyzed by NMR, showing the shape complementarity of the Pa fitting with Q. The structurally unique base Pa provides valuable information for the development of unnatural base pairs toward the expansion of the genetic alphabet.