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Pairing geometry of the hydrophobic thymine analogue 2,4-difluorotoluene in duplex DNA as analyzed by X-ray crystallography.

ABSTRACT: Certain DNA polymerases (pols) were found to efficiently insert A opposite the hydrophobic T isostere 2,4-difluorotoluene (F) and vice versa, resulting in the widely held belief that some pols rely on shape rather than H-bonding for accurate replication. Using X-ray crystallography we have analyzed the geometry of F:A pairs in duplex DNA and observed a distance between fluorine and the exocyclic amino group of A that is consistent with a H-bond, thus challenging the assumption that the F analogue is unable to engage in H-bonding as well as the steric hypothesis of DNA replication. Therefore, shape and H-bonding are inherently related, and steric constraints at a pol active site, or conferred by stacking or the DNA backbone conformation, may enable H-bonding by F.

SUBMITTER: Pallan PS

PROVIDER: S-EPMC2757930 | biostudies-literature | 2009 Sep

REPOSITORIES: biostudies-literature

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Pairing geometry of the hydrophobic thymine analogue 2,4-difluorotoluene in duplex DNA as analyzed by X-ray crystallography.

Pallan Pradeep S PS Egli Martin M

Journal of the American Chemical Society 20090901 35

Certain DNA polymerases (pols) were found to efficiently insert A opposite the hydrophobic T isostere 2,4-difluorotoluene (F) and vice versa, resulting in the widely held belief that some pols rely on shape rather than H-bonding for accurate replication. Using X-ray crystallography we have analyzed the geometry of F:A pairs in duplex DNA and observed a distance between fluorine and the exocyclic amino group of A that is consistent with a H-bond, thus challenging the assumption that the F analogu ...[more]

PMID: 19685868

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