TY - JOUR
T1 - Inhibition of pre-miRNA-136 processing by Dicer with small molecule BzDANP suggested the formation of ternary complex of pre-miR-136–BzDANP–Dicer
AU - Otabe, Takahiro
AU - Nagano, Konami
AU - Kawai, Gota
AU - Murata, Asako
AU - Nakatani, Kazuhiko
N1 - Funding Information:
Part of works described here was supported by JSPS KAKENHI Grant-in-Aid for Specially Promoted Research ( 26000007 ) for KN, for Scientific Research (C) ( 15K01820 ) to AM, and by the Research Program of “Dynamic Alliance for Open Innovation Bridging Human, Environment and Materials” in “Network Joint Research Center for Materials and Devices”.
Publisher Copyright:
© 2019 Elsevier Ltd
PY - 2019/5/15
Y1 - 2019/5/15
N2 - Small-molecule modulators, along with antisense oligonucleotide, would be powerful tools and potential drug candidates for modulating miRNA-related gene expressions. The mechanism of the inhibitory effect of the C-bulge binding small molecule BzDANP for the Dicer processing reaction of pre-miR-136 was discussed on the data obtained by SPR, NMR, and kinetic analysis for Dicer processing. SPR and NMR analysis showed the preference of BzDANP binding to the C-bulge. Michaelis-Menten analysis suggested the formation of a ternary complex pre-miR-136–BzDANP–Dicer during the Dicer-cleavage reaction of pre-miR-136 in the presence of BzDANP. The inhibitory effect of BzDANP is likely attributed to the slower reaction from the ternary complex than that from the binary pre-miR-136–Dicer complex.
AB - Small-molecule modulators, along with antisense oligonucleotide, would be powerful tools and potential drug candidates for modulating miRNA-related gene expressions. The mechanism of the inhibitory effect of the C-bulge binding small molecule BzDANP for the Dicer processing reaction of pre-miR-136 was discussed on the data obtained by SPR, NMR, and kinetic analysis for Dicer processing. SPR and NMR analysis showed the preference of BzDANP binding to the C-bulge. Michaelis-Menten analysis suggested the formation of a ternary complex pre-miR-136–BzDANP–Dicer during the Dicer-cleavage reaction of pre-miR-136 in the presence of BzDANP. The inhibitory effect of BzDANP is likely attributed to the slower reaction from the ternary complex than that from the binary pre-miR-136–Dicer complex.
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U2 - 10.1016/j.bmc.2019.03.031
DO - 10.1016/j.bmc.2019.03.031
M3 - Article
C2 - 30952388
AN - SCOPUS:85063668717
SN - 0968-0896
VL - 27
SP - 2140
EP - 2148
JO - Bioorganic and Medicinal Chemistry
JF - Bioorganic and Medicinal Chemistry
IS - 10
ER -