Structure/affinity studies in the bicyclo-DNA series: Synthesis and properties of oligonucleotides containing bc(en)-T and iso-tricyclo-T nucleosides.
Beilstein J Org Chem
; 10: 1840-7, 2014.
Article
em En
| MEDLINE
| ID: mdl-25161745
ABSTRACT
We present the synthesis of the two novel nucleosides iso-tc-T and bc(en)-T, belonging to the bicyclo-/tricyclo-DNA molecular platform. In both modifications the torsion around C6'-C7' within the carbocyclic ring is planarized by either the presence of a C6'-C7' double bond or a cyclopropane ring. Structural analysis of these two nucleosides by X-ray analysis reveals a clear preference of torsion angle γ for the gauche orientation with the furanose ring in a near perfect 2'-endo conformation. Both modifications were incorporated into oligodeoxynucleotides and their thermal melting behavior with DNA and RNA as complements was assessed. We found that the iso-tc-T modification was significantly more destabilizing in duplex formation compared to the bc(en)-T modification. In addition, duplexes with complementary RNA were less stable as compared to duplexes with DNA as complement. A structure/affinity analysis, including the already known bc-T and tc-T modifications, does not lead to a clear correlation of the orientation of torsion angle γ with DNA or RNA affinity. There is, however, some correlation between furanose conformation (N- or S-type) and affinity in the sense that a preference for a 3'-endo like conformation is associated with a preference for RNA as complement. As a general rule it appears that T m data of single modifications with nucleosides of the bicyclo-/tricyclo-DNA platform within deoxyoligonucleotides are not predictive for the stability of fully modified oligonucleotides.
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01-internacional
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MEDLINE
Idioma:
En
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Beilstein J Org Chem
Ano de publicação:
2014
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Article
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