Synthetic nucleic acid secondary structures containing the four stereoisomers of 1,4-bis(thymine-1-yl)butane-2,3-diol.
The four stereoisomers of the double-headed acyclic nucleoside 1,4-bis(thymine-1-yl)butane-2,3-diol were incorporated in the central position of four 13-mer oligonucleotides. The phosphoramidite building blocks were synthesized in four or six steps from either D- or L-2,3-O-isopropylidenethreitol. Two epimeric and fully deprotected double-headed nucleosides were analyzed by X-ray crystallography. The incorporation into oligonucleotides was hampered by steric hindrance and formation of a cyclic phosphate. The use of pyridinium chloride as the activator and a kinetic analysis based on 31P NMR of the coupling and detritylation processes led to improved yields of the oligonucleotides. In comparison with the (S)-GNA monomer, one of the four stereoisomers was found to show a similar destabilization of a DNA duplex, indicating that the additional base can be introduced without a thermal penalty. Another stereoisomer was found to induce a thermal stabilization of a DNA:RNA three-way junction. Thus, the stereochemistry of this acyclic double-headed nucleoside motif is important, indicating potential for the design of artificial nucleic acid secondary structures.
Christensen
Mikkel S
MS
Nucleic Acid Center, University of Southern Denmark, 5230 Odense M, Denmark.
Bond
Andrew D
AD
Nielsen
Poul
P
D020137:Base Pair Mismatch; D001483:Base Sequence; D002072:Butylene Glycols / Q000737:chemistry*; D018360:Crystallography, X-Ray; D018076:DNA, Complementary / Q000737:chemistry; D005990:Glycerol / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D009690:Nucleic Acid Conformation; D009841:Oligonucleotides / Q000138:chemical synthesis* / Q000737:chemistry*; D012313:RNA / Q000737:chemistry; D013237:Stereoisomerism; D013941:Thymine / Q000031:analogs & derivatives* / Q000737:chemistry*; D044366:Transition Temperature
C527296:1,4-bis(thymin-1-yl)butane-2,3-diol; D002072:Butylene Glycols; D018076:DNA, Complementary; D009841:Oligonucleotides; D012313:RNA; D005990:Glycerol; D013941:Thymine