Base pairing of anhydrohexitol nucleosides with 2,6-diaminopurine, 5-methylcytosine and uracil asbase moiety.
Hexitol nucleic acids (HNAs) with modified bases (5-methylcytosine, 2,6-diaminopurine or uracil) were synthesized. The introduction of the 5-methylcytosine base demonstrates that N -benzoylated 5-methylcytosyl-hexitol occurs as the imino tautomer. The base pairing systems (G:CMe, U:D, T:D and U:A) obey Watson-Crick rules. Substituting hT for hU, hCMefor hC and hD for hA generally leads to increased duplex stability. In a single case, replacement of hC by hCMedid not result in duplex stabilization. This sequence-specific effect could be explained by the geometry of the model duplex used for carrying out the thermal stability study. Generally, polypurine HNA sequences give more stable duplexes with their RNA complement than polypyrimidine HNA sequences. This observation supports the hypothesis that, besides changes in stacking pattern, the difference in conformational stress between purine and pyrimidine nucleosides may contribute to duplex stability. Introduction of hCMeand hD in HNA sequences further increases the potential of HNA to function as a steric blocking agent.
Laboratory of Medicinal Chemistry, Rega Institute for Medical Research, Katholieke Universiteit Leuven, Minderbroedersstraat 10, B-3000 Leuven, Belgium.
V
V
Boudou
L
L
Kerremans
B
B
De Bouvere
E
E
Lescrinier
G
G
Schepers
R
R
Busson
A
A
Van Aerschot
P
P
Herdewijn
D015075:2-Aminopurine / Q000031:analogs & derivatives* / Q000737:chemistry; D044503:5-Methylcytosine; D001087:Arabinonucleosides / Q000737:chemistry; D020029:Base Pairing; D003596:Cytosine / Q000031:analogs & derivatives* / Q000737:chemistry; D008958:Models, Molecular; D009691:Nucleic Acid Denaturation; D009705:Nucleosides / Q000737:chemistry*; D009841:Oligonucleotides / Q000138:chemical synthesis; D011684:Purine Nucleosides / Q000737:chemistry; D011741:Pyrimidine Nucleosides / Q000737:chemistry; D013402:Sugar Alcohols / Q000737:chemistry; D014498:Uracil / Q000031:analogs & derivatives*
D001087:Arabinonucleosides; D009705:Nucleosides; D009841:Oligonucleotides; D011684:Purine Nucleosides; D011741:Pyrimidine Nucleosides; D013402:Sugar Alcohols; D015075:2-Aminopurine; C007300:2,6-diaminopurine; D014498:Uracil; D044503:5-Methylcytosine; D003596:Cytosine