抑制丙型肝炎病毒NS3蛋白酶和螺旋酶活性的高效双功能适体的设计与分析

Designing and analysis of a potent bi-functional aptamers that inhibit protease and helicase activities of HCV NS3.

作者信息

Umehara Takuya, Fukuda Kotaro, Nishikawa Fumiko, Sekiya Satoru, Kohara Michinori, Hasegawa Tsunemi, Nishikawa Satoshi

机构信息

Institute of Biological Resources and Functions, National Institute of Advanced Industrial Science and Technology, Tsukuba, Ibaraki 305-8566, Japan.

出版信息

Nucleic Acids Symp Ser (Oxf). 2004(48):195-6. doi: 10.1093/nass/48.1.195.

DOI:10.1093/nass/48.1.195

PMID:17150545

Abstract

Nonstructural protein 3 (NS3) of hepatitis C virus (HCV) is a multi-functional enzyme having protease and helicase activities. NS3 is essential for HCV replication and proliferation. Previously, we obtained RNA aptamers against NS3 protease domain (Protease aptamer; deltaNEO-III and G9-II) and helicase domain (helicase aptamer; #5), and they inhibited the enzyme activities, respectively. We designed and constructed new bi-functional aptamers NEO-35-sX and G925-sX (X: 5-51 nts) by conjugating protease and helicase aptamers via oligo U spacer. Some of them showed 10-fold higher helicase inhibition than helicase aptamer #5 alone.

摘要

丙型肝炎病毒（HCV）的非结构蛋白3（NS3）是一种具有蛋白酶和解旋酶活性的多功能酶。NS3对于HCV的复制和增殖至关重要。此前，我们获得了针对NS3蛋白酶结构域（蛋白酶适体；deltaNEO-III和G9-II）和解旋酶结构域（解旋酶适体；#5）的RNA适体，它们分别抑制了酶的活性。我们通过寡聚U间隔区连接蛋白酶适体和解旋酶适体，设计并构建了新的双功能适体NEO-35-sX和G925-sX（X：5-51个核苷酸）。其中一些双功能适体对解旋酶的抑制作用比单独的解旋酶适体#5高10倍。