title: Base-pairing, tautomerism, and mismatch discrimination of 7-halogenated 7-deaza-2'-deoxyisoguanosine: oligonucleotide duplexes with parallel and antiparallel chain orientation.
abstract: Oligonucleotides containing 2'-deoxyisoguanosine (1, iG(d)), 7-deaza-2'-deoxyisoguanosine (2, c(7)iG(d)), and its 7-halogenated derivatives 3 and 4 were synthesized on solid phase using the phosphoramidite building blocks 5-7. The hybridization properties of oligonucleotides were studied on duplexes with parallel and antiparallel chain orientation. It was found that the 7-halogenated nucleoside analogues 3 and 4 enhance the duplex stability significantly in both parallel (ps) and antiparallel (aps) DNA. Moreover, the halogenated nucleosides shift the tautomeric keto-enol equilibrium strongly toward the keto form, with K(TAUT) [keto]/[enol] approximately 10(4) coming close to that of 2'-deoxyguanosine (10(4)-10(5)), while the nonhalogenated 7-deaza-2'-deoxyisoguanosine 2 shows a K(TAUT) of around 2000 and the enol concentration of 1 is 10% in aqueous solution. Consequently, nucleosides 3 and 4 show a much better mismatch discrimination against dT than compound 1 or 2 in antiparallel as well as in parallel DNA. 3 and 4 are expected to increase the selectivity of base incorporation opposite to isoC(d) in the form of triphosphates or in the polymerase-catalyzed reaction in comparison to 1 or 2.
authors.affiliation: Laboratorium für Organische und Bioorganische Chemie, Institut für Chemie, Universität Osnabrück, Barbarastrasse 7, D-49069 Osnabrück, Germany. Frank.Seela@uni-osnabrueck.de
authors.forename: Frank
authors.initials: F
authors.lastname: Seela
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Peng
authors.forename: Hong
authors.initials: H
authors.lastname: Li
mesh_terms: D020137:Base Pair Mismatch; D020029:Base Pairing; D018360:Crystallography, X-Ray; D004247:DNA / Q000737:chemistry / Q000235:genetics; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000235:genetics; D007700:Kinetics; D019906:Nuclear Magnetic Resonance, Biomolecular; D009841:Oligonucleotides / Q000138:chemical synthesis / Q000737:chemistry* / Q000235:genetics; D009943:Organophosphorus Compounds / Q000138:chemical synthesis / Q000737:chemistry; D013816:Thermodynamics
chemical_list: D009841:Oligonucleotides; D009943:Organophosphorus Compounds; C434331:phosphoramidite; D004247:DNA; D003849:Deoxyguanosine