title: Synthesis and conformational dynamics of the reported structure of xylopyridine A.
abstract: Natural products have served as a rich source for the discovery of new nucleic acid targeting molecules for more than half a century. However, our ability to design molecules that bind nucleic acid motifs in a sequence- and/or structure-selective manner is still in its infancy. Xylopyridine A, a naturally occurring molecule of unprecedented architecture, has been found to bind DNA by a unique mode of intercalation. Here we show that the structure proposed for xylopyridine A is not consistent with the characterization in the original isolation report and does not bind B-form DNA. Instead, we report that the originally proposed structure for xylopyridine A represents a new class of conformationally dynamic structure-selective quadruplex nucleic acid binder. The unique molecular conformation locks out nonspecific intercalative binding modes and provides a starting point for the design of a new class of structure-specific nucleic acid binder.
authors.affiliation: Department of Chemistry, University of Pennsylvania, 231 South 34th Street, Philadelphia, Pennsylvania 19104-6323, USA.
authors.forename: Robert-André F
authors.initials: RA
authors.lastname: Rarig
authors.forename: Mai N
authors.initials: MN
authors.lastname: Tran
authors.forename: David M
authors.initials: DM
authors.lastname: Chenoweth
mesh_terms: D004247:DNA / Q000378:metabolism*; D007364:Intercalating Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D008958:Models, Molecular; D011725:Pyridines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D044004:Xanthones / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D013098:Xylariales / Q000737:chemistry*
chemical_list: D007364:Intercalating Agents; D011725:Pyridines; D044004:Xanthones; C585776:xylopyridine A; D004247:DNA