TY - JOUR
T1 - Synthesis of peptide nucleic acids (PNA) with a crosslinking agent to RNA and effective inhibition of dicer
AU - Akisawa, Takuya
AU - Yamada, Ken
AU - Nagatsugi, Fumi
N1 - Funding Information:
This work was supported by a Grant-in-Aid for Scientific Research on Innovative Areas (“Middle Molecular Strategy.” JP15H05838 ) and a Grant-in-Aid for Scientific Research (B) [ 25288073 ] from the Japan Society for the Promotion of Science (JSPS). This work was also supported in part by the research program of “Dynamic Alliance for Open Innovation Bridging Human, Environment and Materials”.
Publisher Copyright:
© 2016 Elsevier Ltd
PY - 2016
Y1 - 2016
N2 - Peptide nucleic acids (PNAs) are structural mimics of nucleic acids that form stable hybrids with DNA and RNA. Due to these characteristics, PNAs are widely used as biochemical tools, for example, in antisense/antigene therapy. In this study, we have synthesized PNAs incorporating 2-amino-6-vinylpurine (AVP) for the covalent targeting of single-stranded DNA and RNA, and evaluated their reactivities for these targets. PNA containing AVP at the N-terminal position showed a high reactivity to uracil in RNA and thymine in DNA at the complementary site with AVP. In addition, the crosslinking reactions to pre-miR122 with PNA containing AVP increased the inhibition effect for the Dicer processing of pre-miR122 in vitro.
AB - Peptide nucleic acids (PNAs) are structural mimics of nucleic acids that form stable hybrids with DNA and RNA. Due to these characteristics, PNAs are widely used as biochemical tools, for example, in antisense/antigene therapy. In this study, we have synthesized PNAs incorporating 2-amino-6-vinylpurine (AVP) for the covalent targeting of single-stranded DNA and RNA, and evaluated their reactivities for these targets. PNA containing AVP at the N-terminal position showed a high reactivity to uracil in RNA and thymine in DNA at the complementary site with AVP. In addition, the crosslinking reactions to pre-miR122 with PNA containing AVP increased the inhibition effect for the Dicer processing of pre-miR122 in vitro.
KW - Crosslink
KW - Dicer
KW - Invasion
KW - Peptide nucleic acid
KW - miRNA
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U2 - 10.1016/j.bmcl.2016.11.002
DO - 10.1016/j.bmcl.2016.11.002
M3 - Article
C2 - 27838183
AN - SCOPUS:84997820336
SN - 0960-894X
VL - 26
SP - 5902
EP - 5906
JO - Bioorganic and Medicinal Chemistry Letters
JF - Bioorganic and Medicinal Chemistry Letters
IS - 24
ER -