Synthesis and pairing properties of oligonucleotides containing 3-hydroxy-4-hydroxymethyl-1-cyclohexanyl nucleosides

Citation
Y. Maurinsh et al., Synthesis and pairing properties of oligonucleotides containing 3-hydroxy-4-hydroxymethyl-1-cyclohexanyl nucleosides, CHEM-EUR J, 5(7), 1999, pp. 2139-2150
Citations number
25
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Chemistry
Journal title
CHEMISTRY-A EUROPEAN JOURNAL
ISSN journal
0947-6539 → ACNP
Volume
5
Issue
7
Year of publication
1999
Pages
2139 - 2150
Database
ISI
SICI code
0947-6539(199907)5:7<2139:SAPPOO>2.0.ZU;2-C
Abstract
The enantiomeric forms of cyclohexanyl adenine and thymine nucleosides were obtained by separation of their diastereomeric esters with (R)-(-)methylma ndelic acid. The four nucleoside analogues were appropriately protected, co nverted to their phosphoramidites and oligomerized. The resulting cyclohexa nyl nucleic acids (CNAs) represent a new enantioselective Watson-Crick base -pairing system. Homochiral oligomers of equivalent chirality show Watson-C rick pairing, while those of opposite chirality (D-CNA and L-CNA) do not. N o isochiral or heterochiral adenine-adenine or thymine-thymine base pairing is observed. Complex formation occurs only between oligomers in antiparall el orientations. D-CNA hybridizes with natural nucleic acids, and the stren gth of the interaction decreases in the order dsCNA>CNA:RNA> CNA:DNA. Thus, the D-cyclohexanyl nucleic acids are RNA-selective. L-CNA hybridizes eithe r very weakly or not at all with natural nucleic acids, and the nature of t his association is not clear. This study of CNAs leads us to hypothesize th at a) the conformation of a single nucleoside analogue may be different fro m its conformation in an oligonucleotide and b) the conformational stress o f a nucleotide analogue incorporated in an oligomer may contribute to the s equence-dependent thermal stability of oligonucleotide complexes.