Structural analysis of telomere G-quartet and molecular design of new nucleic acid aptamer
| Project/Area Number |
15570098
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Structural biochemistry
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| Research Institution | Kyoto Institute of Technology |
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Principal Investigator |
KANAORI Kenji Kyoto Institute of Technology, Faculty of Textile, Associate Professor, 繊維学部, 助教授 (30273543)
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2004: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2003: ¥2,700,000 (Direct Cost: ¥2,700,000)
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| Keywords | telomere / four stranded structure / nucleic acid aptamer / i-moitf / G-quartet / NMR |
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| Research Abstract |
The P-chiral stereodefined phosphorothioate groups have been introduced into all the four internucleotide positions of d(T_<PS1>C_<PS2>C_<PS3>C_<PS4>C) (PSn : phosphorothioate group), and among possible 16 diastereomers of PS-d(TC_4), 10 stereomers have been synthesized to investigate the effects of the sense of the P-chirality upon the structure and stability of the i-motif structure. The temperature dependence of circular dichroism spectra showed melting temperature (Tm) of the [all R_p]PS-d(TC_4) i-motif was 31 ℃ identical to that of the parent oligomer, PO-d(TC_4), while that of the [all S_p]PS-d(TC_4) i-motif was largely decreased by 11℃. Single substitution of R_p with S_p caused a decrease of T_m by 3〜4℃ at positions of PS1, 2, and 3, and by 1℃ at that of PS4, showing the additive property of the T_m suppression. The comparison of the NOESY spectra between [all R_p]PS-, [all S_p]PS-, and PO-d(TC_4) showed that intra-residual H6-H3' and H2"-H4' NOE cross-peaks of the [all S_p] isomer are weaker than those of the [all R_p] isomer and PO-d(TC_4), indicating the change in the C3'-endo conformation and glycosidic bond angle. The structural alternation for the i-motif formed by [all S_p]PS-d(TC_4) is also suggested by the chemical shift differences of C2/C3/C4 H2"and H4' protons from those of [all R_p]PS-d(TC_4) and PO-d(TC_4). These results suggest that the S_p configuration at phosphorus of the phosphorothioate linkage change the sugar-phosphorothioate conformation and intermolecular interaction in the narrow groove, leading to the destabilization of the i-motif structure.
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Report
(3 results)
Research Products
(16 results)
