MEDI 339 |
| G-tetrads are unusual structures that result from the self-association of guanosines. In the present work, we focus on the relationship between sugar pucker and the alternating syn-anti base orientation of guanine bases in G-tetrads. We have incorporated North and South bicyclo[3.1.0]hexane nucleosides on the thrombin binding aptamer [d(G2T2G2TGTG2T2G2)] as a model of an intramolecular anti-parallel G-tetrad, by alternating locked North- and South-methanocarba-deoxyguanosines in two sequences. The first sequence mimics the naturally observed pattern beginning with a syn-South-G, while the second has the opposite orientation beginning with an anti-North-G. The middle TGT and all the T's are natural nucleosides. We expect the modified oligonucleotides would be effective in either promoting or inhibiting the proper folding by affecting the local and global conformation. The corresponding North-type and South-type guanosine phosphoramidites and solid supports for DNA synthesis were successfully prepared. The chemical synthesis and biophysical properties will be presented. |
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Poster Session
7:00 PM-9:00 PM, Wednesday, August 22, 2007 BCEC -- Exhibit Hall - B2, Poster
Division of Medicinal Chemistry |