title: Pyrenylmethyldeoxyadenosine: a 3'-cap for universal DNA hybridization probes.
abstract: A ligand that stabilizes a three-dimensional structure can be expected to have a positive effect on the specificity with which this structure is formed. Here we report on a ligand covalently linked to an oligonucleotide that increases duplex stability, but decreases base-pairing selectivity at the terminus. The ligand consists of a dangling 2'-deoxyadenosine residue with a pyrenylmethyl substituent at the N6-position, that is, a deoxynucleoside with a covalently linked polycyclic aromatic hydrocarbon (PAH). In the presence of the pyrene-bearing nucleosides the UV melting point (DeltaT(m)) of duplexes increases by up to 29.1 degrees C. The modified residue lowers the base-pairing fidelity at the terminal and penultimate position of duplexes with a depression in DeltaDeltaT(m) observable in 20 out of 24 sequence contexts tested. The effect can be rationalized based on a modeled three-dimensional structure. The results are significant for the understanding of base-pairing fidelity in DNA duplexes as modulated by the presence of a polycyclic aromatic hydrocarbon. The fidelity-decreasing effect may be useful for universal hybridization probes that bind to a broader range of sequences than conventional oligonucleotides.
authors.affiliation: Institut für Organische Chemie, Universität Karlsruhe (TH), 76131 Karlsruhe, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Printz
authors.forename: Clemens
authors.initials: C
authors.lastname: Richert
mesh_terms: D020029:Base Pairing; D001483:Base Sequence; D015342:DNA Probes / Q000737:chemistry*; D003839:Deoxyadenosines / Q000138:chemical synthesis / Q000737:chemistry*; D009693:Nucleic Acid Hybridization; D044367:Phase Transition; D011084:Polycyclic Aromatic Hydrocarbons / Q000737:chemistry; D011721:Pyrenes / Q000138:chemical synthesis / Q000737:chemistry*; D013696:Temperature
chemical_list: D015342:DNA Probes; D003839:Deoxyadenosines; D011084:Polycyclic Aromatic Hydrocarbons; D011721:Pyrenes; C540665:pyrenylmethyldeoxyadenosine