Structure/affinity studies in the bicyclo-DNA series: Synthesis and properties of oligonucleotides containing bcen-T and iso-tricyclo-T nucleosides
Data(s) |
12/08/2014
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Resumo |
We present the synthesis of the two novel nucleosides iso-tc-T and bcen-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 bcen-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 Tm data of single modifications with nucleosides of the bicyclo-/tricyclo-DNA platform within deoxyoligonucleotides are not predictive for the stability of fully modified oligonucleotides. |
Formato |
application/pdf |
Identificador |
http://boris.unibe.ch/57940/1/1860-5397-10-194.pdf Dugovic, Branislav; Wagner, Michael; Leumann, Christian J. (2014). Structure/affinity studies in the bicyclo-DNA series: Synthesis and properties of oligonucleotides containing bcen-T and iso-tricyclo-T nucleosides. Beilstein journal of organic chemistry, 10, pp. 1840-1847. Beilstein-Institut 10.3762/bjoc.10.194 <http://dx.doi.org/10.3762/bjoc.10.194> doi:10.7892/boris.57940 info:doi:10.3762/bjoc.10.194 urn:issn:1860-5397 |
Idioma(s) |
eng |
Publicador |
Beilstein-Institut |
Relação |
http://boris.unibe.ch/57940/ |
Direitos |
info:eu-repo/semantics/openAccess |
Fonte |
Dugovic, Branislav; Wagner, Michael; Leumann, Christian J. (2014). Structure/affinity studies in the bicyclo-DNA series: Synthesis and properties of oligonucleotides containing bcen-T and iso-tricyclo-T nucleosides. Beilstein journal of organic chemistry, 10, pp. 1840-1847. Beilstein-Institut 10.3762/bjoc.10.194 <http://dx.doi.org/10.3762/bjoc.10.194> |
Palavras-Chave | #570 Life sciences; biology #540 Chemistry |
Tipo |
info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion PeerReviewed |