Alpha- and beta-stilbenosides as base-pair surrogates in DNA hairpins.
The synthesis, structure, and optical spectroscopy of hairpin oligonucleotide conjugates possessing synthetic stilbene C-nucleosides (stilbenosides) are reported. Synthetic methods for selective preparation of both the alpha- and beta-stilbenosides have been developed. Both anomers are effective in stabilizing hairpin structures when used as capping groups at the open end of the hairpin base-pair domain. However, only the beta-anomer effectively stabilizes the hairpin structure when located in the interior of the base-pair domain opposite an abasic site. Similar results are obtained for hairpins possessing two stilbenosides, either adjacent to each other or with one intervening base-pair. Molecular dynamics simulations are employed to obtain averaged structures for these conjugates. The calculated structures for the capped hairpins formed with either anomer show effective pi-stacking with the adjacent base-pair. The calculated structures for the internal stilbenosides show that the alpha- and beta-anomers form extrahelical and intrahelical structures, respectively. The relative orientations of the two stilbenes in the bis-stilbenosides have been studied using a combination of exciton-coupled circular dichroism spectroscopy and molecular modeling.
Zhang
Ligang
L
Department of Chemistry, Northwestern University, Evanston, IL 60201, USA.
Long
Hai
H
Boldt
Grant E
GE
Janda
Kim D
KD
Schatz
George C
GC
Lewis
Frederick D
FD
D020029:Base Pairing; D002942:Circular Dichroism; D004247:DNA / Q000737:chemistry*; D008958:Models, Molecular; D009690:Nucleic Acid Conformation; D009705:Nucleosides / Q000138:chemical synthesis* / Q000737:chemistry; D013267:Stilbenes / Q000737:chemistry*
D009705:Nucleosides; D013267:Stilbenes; D004247:DNA