Dependence of aptamer activity on opposed terminal extensions: improvement of light-regulation efficiency

被引：64

作者：

Buff, Maximilian C. R. ^{[1
]}

Schäfer, Florian ^{[1
]}

Wulffen, Bernhard ^{[2
,3
]}

Mueller, Jens ^{[4
]}

Potzsch, Bernd ^{[4
]}

Heckel, Alexander ^{[1
]}

Mayer, Gunter ^{[2
,3
]}

机构：

[1] Goethe Univ Frankfurt, Cluster Excellence Macromol Complexes, D-60438 Frankfurt, Germany

[2] Univ Strathclyde, Strathclyde Inst Pharm & Biol Sci, Glasgow G4 0NR, Lanark, Scotland

[3] Univ Bonn, D-53121 Bonn, Germany

[4] Univ Hosp Bonn, Inst Expt Haematol & Transfus Med, D-53127 Bonn, Germany

来源：

NUCLEIC ACIDS RESEARCH | 2010年 / 38卷 / 06期

关键词：

BIVALENT APTAMER; DNA APTAMER; THROMBIN; ANTICOAGULANT; OLIGONUCLEOTIDES; STABILITY; MOLECULES; SEQUENCE;

D O I：

10.1093/nar/gkp1148

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Aptamers that can be regulated with light allow precise control of protein activity in space and time and hence of biological function in general. In a previous study, we showed that the activity of the thrombin-binding aptamer HD1 can be turned off by irradiation using a light activatable 'caged' intramolecular antisense-domain. However, the activity of the presented aptamer in its ON state was only mediocre. Here we studied the nature of this loss in activity in detail and found that switching from 5'- to 3'-extensions affords aptamers that are even more potent than the unmodified HD1. In particular we arrived at derivatives that are now more active than the aptamer NU172 that is currently in phase 2 clinical trials as an anticoagulant. As a result, we present light-regulatable aptamers with a superior activity in their ON state and an almost digital ON/OFF behavior upon irradiation.

引用

页码：2111 / 2118

页数：8

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