Acyclic, achiral enamide nucleoside analogues. The importance of the C=C bond in the analogue for its ability to mimic natural nucleosides.
The conformations of an acyclic, achiral enamide thymidine analogue 1 have been studied by model building and geometry calculations, as well as by NMR NOE and UV experiments. The results indicate that there are no significant barriers to rotation around any of the sigma bonds, in particular the N1-C1' enamide bond, and that the analogue should be able to accommodate conformations that mimic the conformations of natural nucleosides in A- and B-type helices quite well. For comparison the saturated analogue 2 has been prepared and built into oligonucleotides. It is shown that incorporation of 2 in oligonucleotides results in a much larger depression of the melting temperature (deltaTm -10 to -12.5 degrees C) than does incorporation of 1 (deltaTm -5 to -6.5 degrees C).
Department of Chemistry, University of Copenhagen, The H. C. Orsted Institute, Universitetsparken 5, DK-2100 Copenhagen, Denmark.
Asger B
AB
Petersen
Michael A
MA
Petersen
Ulla
U
Henriksen
Steen
S
Hammerum
Otto
O
Dahl
D040761:Biomimetic Materials / Q000138:chemical synthesis* / Q000737:chemistry*; D002244:Carbon / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008968:Molecular Conformation; D015394:Molecular Structure; D009691:Nucleic Acid Denaturation; D009693:Nucleic Acid Hybridization; D009711:Nucleotides / Q000138:chemical synthesis* / Q000737:chemistry*; D013057:Spectrum Analysis; D013237:Stereoisomerism; D013936:Thymidine / Q000737:chemistry
D009711:Nucleotides; D002244:Carbon; D013936:Thymidine