title: B- to Z-DNA transition probed by oligonucleotides containing methylphosphonates.
abstract: The simulation of the B--Z-DNA transition by using space-filling models of the dimer d(C-G) shows the possibility of hydrogen-bond formation between the N-2 amino group of the partially rotated guanine and one of the 5'-phosphate oxygens of deoxyguanylic acid. To probe the importance of this postulated interaction, analogs of the hexamer d(C-G)3 were synthesized. These analogs contained a methylphosphonate linkage, of distinct stereochemistry, which replaced the first 5'-phosphate linkage of deoxyguanosine. The CD spectra in high salt concentration showed that the hexamer containing a methylphosphonate linkage with the RP stereochemistry formed Z-DNA to the same extent as d(C-G)3, whereas the hexamer containing a methylphosphonate linkage with the SP stereochemistry did not form Z-DNA. These results are consistent with a mechanism in which an interaction between the N-2 amino group of guanine and the prochiral SP oxygen of deoxyguanosine 5'-phosphate kinetically controls the formation of Z-DNA. A water bridge between the N-2 amino group of guanine and the 3'-phosphate oxygen of deoxyguanylic acid has been implicated in the stabilization of Z-DNA. To probe the importance of this water bridge, two additional analogs of the hexamer d(C-G)3 were synthesized. These analogs contained a methylphosphonate linkage, of distinct stereochemistry, that replaced the first deoxyguanosine 3'-phosphate. The CD spectra showed that the hexamer containing a methylphosphonate linkage of the RP stereochemistry underwent the transition to Z-DNA to the same extent as d(C-G)3, whereas the hexamer containing a methylphosphonate linkage of the SP stereochemistry underwent the transition to Z-DNA to a 35% lesser extent. Thus the water bridge involving the prochiral SP oxygen provides modest stabilization energy for Z-DNA. These studies, therefore, suggest that the B--Z-DNA transition is regulated both thermodynamically and kinetically through hydrogen-bond interactions involving phosphate oxygens and the N-2 amino group of guanine.
authors.forename: L
authors.initials: L
authors.lastname: Callahan
authors.forename: F S
authors.initials: FS
authors.lastname: Han
authors.forename: W
authors.initials: W
authors.lastname: Watt
authors.forename: D
authors.initials: D
authors.lastname: Duchamp
authors.forename: F J
authors.initials: FJ
authors.lastname: Kézdy
authors.forename: K
authors.initials: K
authors.lastname: Agarwal
mesh_terms: D001482:Base Composition; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D002942:Circular Dichroism; D003460:Crystallization; D004247:DNA / Q000378:metabolism*; D007700:Kinetics; D008958:Models, Molecular; D009690:Nucleic Acid Conformation; D009838:Oligodeoxyribonucleotides / Q000378:metabolism*; D009841:Oligonucleotides / Q000378:metabolism; D063065:Organophosphonates / Q000378:metabolism*; D009994:Osmolar Concentration; D012996:Solutions
chemical_list: D009838:Oligodeoxyribonucleotides; D009841:Oligonucleotides; D063065:Organophosphonates; D012996:Solutions; D004247:DNA