Biomedical Engineering Reference
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Fig. 3.6
Global and local structures of the 2-Se-T-DNA [(5
0
-GdU2
0
-Se- G-SeT-ACAC-3
0
)
2
], with
a resolution of 1.58 A. (
a
) The superimposed comparison of the Se-DNA duplex (3HGD, in
green
)
with its native counterpart (1D78, in
cyan
). The
red
balls represent the selenium atoms. (
b
)The
superimposed comparison of the local
2Se
T4/A5 (in
green
) and native T4/A5 (in
cyan
) base pairs.
(
c
) The experimental electron density map of the SeT4/A5 base pair
3.4.2.3
2-Selenouridine
Similar to 2-thio-RNA derivatives, selenium-modified tRNAs are naturally occur-
ring RNAs in bacteria, such as
Escherichia coli
and
Clostridium sticklandii
[
83
].
This type of Se modification was first found at the wobble position of the anticodon
loop of tRNA [
84
]. Later, it was identified as 5-methylaminometnyl-2-selenouridine
(mmm5Se2U) [
85
]. Though it has been proposed that this selenium modification on
tRNAs may help to improve the translational efficiency and accuracy, the detailed
mechanism is still unclear. Our recent investigation on the synthesis and biophysical
property of the 2-Se-U-RNAs will help to better understand the mechanism of the
natural Se modification [
17
].
Recently, the synthesis of the 2-Se-U phosphoramidite (Scheme
3.9
) was also
achieved by taking advantage of the Huang reaction [
17
,
18
] to incorporate the
selenium functionality into uridine, similar to the 2-Se-T synthesis. The 5
0
-and
2
0
-hydroxyl groups were protected before the phosphoramidite synthesis. The
2-Se-U-oligonucleotides could be prepared by standard ultra-mild RNA synthesis
and purification protocols. UV denaturing experiment results suggest that the
2-Se-U modification can significantly discriminate against U/G wobble pair in
two ways: destabilizing the U/G wobble pair and stabilizing Watson-Crick U/A
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