The new strategy for the development of the inhibitor of reverse transcriptase

2016 Fiscal Year Final Research Report

• Project/Area Number: 15K14975
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Drug development chemistry
• Research Institution: Tohoku University
• Principal Investigator: Nagatsugi Fumi 東北大学, 多元物質科学研究所, 教授 (90208025)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Keywords: 逆転写阻害核酸系薬剤 / 薬剤耐性機構 / HIV治療薬 / ヌクレオチド除去反応 / 架橋反応

Outline of Final Research Achievements

A number of nucleoside (or nucleotide) reverse transcriptase inhibitors (NRTIs) are used in the treatment of HIV and hepatitis B. The long term administration of these medicines is required in this treatment, and leads the appearance of the drug-resistance virus. The major mechanism of resistance to NRTIs is a nucleotide excision, in which is removed of chain-terminating 3’-terminal NRTIs. In this study, we aim to develop the new strategy for the design of the reverse transcriptase inhibitor with drug resistance. We expected that the cross-linking reactions between RNA template and primer DNA would lead the inhibition for the reverse transcriptase reaction by forming covalent bond. We prepared the crosslink forming oligonucleotide (CFO) containing 2-amino-6-vinylpurine (AVP) at 3’ terminal position of the DNA primer. The CFO can react to the target thymine at the complementary site. The crosslinked duplex DNA can inhibit the HIV-1 reverse transcriptase by capturing this enzyme.

Free Research Field

核酸化学、ケミカルバイオロジー