Modulation of BACE1 Activity by Chemically Modified Aptamers

被引：23

作者：

Gasse, Cecile ^{[1
]}

Zaarour, Marwa ^{[1
]}

Noppen, Sam ^{[2
]}

Abramov, Mikhail ^{[3
]}

Marliere, Philippe ^{[4
]}

Liekens, Sandra ^{[2
]}

De Strooper, Bart ^{[5
,6
,7
]}

Herdewijn, Piet ^{[1
,3
]}

机构：

[1] Univ Evry, CNRS, UMR8030, Lab iSSB,CEA,DRF,IG,Univ Paris Saclay,Genoscope, 5 Rue Henri Desbrueres, F-91030 Evry, France

[2] Katholieke Univ Leuven, Rega Inst Med Res, Dept Microbiol & Immunol, Lab Virol & Chemotherapy, Herestr 49,Postbus 1043, B-3000 Leuven, Belgium

[3] Katholieke Univ Leuven, Rega Inst Med Res, Med Chem, Herestr 49, B-3000 Leuven, Belgium

[4] European Syndicate Synthet Scientists & Ind TESSI, 81 Rue Reaumur, F-75002 Paris, France

[5] VIB, Ctr Brain & Dis Res, Herestr 49, B-3000 Leuven, Belgium

[6] Katholieke Univ Leuven, Leuven Inst Neurosci & Dis, Dept Neurosci, Herestr 49, B-3000 Leuven, Belgium

[7] UCL, Dementia Res Inst UK, Gower St, London WC1E 6BT, England

来源：

CHEMBIOCHEM | 2018年 / 19卷 / 07期

基金：

欧洲研究理事会;

关键词：

aptamers; BACE1; inhibitors; secretases; XNA; IN-VITRO SELECTION; EXPANDED GENETIC ALPHABET; ESCHERICHIA-COLI; BETA-SECRETASE; DIRECTED EVOLUTION; SSDNA APTAMERS; RNA CLEAVAGE; DNA APTAMERS; 5-CHLOROURACIL; FUNCTIONALITY;

D O I：

10.1002/cbic.201700461

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：

A modified DNA aptamer that binds BACE1, a therapeutic target involved in Alzheimer's disease has been developed. This ssXNA not only tightly binds to BACE1 but also inhibits its protease activity in vitro in the same range as a previously described unmodified aptamer. We report the in vitro selection of functional oligonucleotides incorporating two nucleobase modifications: 5-chlorouracil and 7-deazaadenine. The nucleoside analogue 5-chloro-2-deoxyuridine has already been explored as a replacement for thymidine in a chemically modified genome of a bacterium. Thus, 5-chlorouracil modification is a good candidate to support genetic transfer in vivo as well as functional activity.

引用

页码：754 / 763

页数：10

共 65 条

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