DNA-Small Molecule Chimera with Responsive Protein-Binding Ability

被引：33

作者：

Harris, D. Calvin ^{[1
]}

Chu, Xiaozhu ^{[1
]}

Jayawickramarajah, Janarthanan ^{[1
]}

机构：

[1] Tulane Univ, Dept Chem, New Orleans, LA 70118 USA

来源：

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY | 2008年 / 130卷 / 45期

关键词：

D O I：

10.1021/ja806552c

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

In this communication, we disclose a generalizable strategy for developing agents with regulable protein-binding ability. In particular, a responsive DNA-small molecule chimera (DC) 1 consisting of two synthetic protein-binding arms and a core oligonucleotide (ODN) domain is discussed. DC 1 can be cycled from a bidentate intramolecular quadruplex form to a monodentate duplex structure, via addition of external ODN stimuli. Importantly, these distinct secondary structures of 1 lead to significantly different protein-binding abilities, with the bidentate conformation showing a 20-fold enhancement (with a 0.8 mu M dissociation constant, K-d) in trypsin-binding potency.

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页码：14950 / +

页数：3

相关论文

共 22 条

[1] DNA duplex-quadruplex exchange as the basis for a nanomolecular machine [J].

Alberti, P ;

Mergny, JL .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2003, 100 (04) :1569-1573

[2] DNA nanomachines and nanostructures involving quadruplexes [J].

Alberti, Patrizia ;

Bourdoncle, Anne ;

Sacca, Barbara ;

Lacroix, Laurent ;

Mergny, Jean-Louis .

ORGANIC & BIOMOLECULAR CHEMISTRY, 2006, 4 (18) :3383-3391

[3] DNA-based machines [J].

Beissenhirtz, Moritz K. ;

Willner, Itamar .

ORGANIC & BIOMOLECULAR CHEMISTRY, 2006, 4 (18) :3392-3401

[4] G-quartets 40 years later:: From 5′-GMP to molecular biology and supramolecular chemistry [J].

Davis, JT .

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 2004, 43 (06) :668-698

[5] A DNA-based machine that can cyclically bind and release thrombin [J].

Dittmer, WU ;

Reuter, A ;

Simmel, FC .

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 2004, 43 (27) :3550-3553

[6] Highly sensitive in vitro selections for DNA-linked synthetic small molecules with protein binding affinity and specificity [J].

Doyon, JB ;

Snyder, TM ;

Liu, DR .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2003, 125 (41) :12372-12373

[7] First-in-human experience of an antidote-controlled anticoagulant using RNA aptamer technology - A phase 1a pharmacodynamic evaluation of a drug-antidote pair for the controlled regulation of factor IXa activity [J].

Dyke, Christopher K. ;

Steinhubl, Steven R. ;

Kleiman, Neal S. ;

Cannon, Richard O. ;

Aberle, Laura G. ;

Lin, Min ;

Myles, Shelley K. ;

Melloni, Chiara ;

Harrington, Robert A. ;

Alexander, John H. ;

Becker, Richard C. ;

Rusconi, Christopher P. .

CIRCULATION, 2006, 114 (23) :2490-2497

[8] Specific protein domains mediate cooperative assembly of HuR oligomers on AU-rich mRNA-destabilizing sequences [J].

Fialcowitz-White, Elizabeth J. ;

Brewer, Brandy Y. ;

Ballin, Jeff D. ;

Willis, Chris D. ;

Toth, Eric A. ;

Wilson, Gerald M. .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2007, 282 (29) :20948-20959

[9]

Li JWJ, 2002, NANO LETT, V2, P315, DOI 10.1021/n1015713+

[10] Crystal structures of human factor Xa complexed with potent inhibitors [J].

Maignan, S ;

Guilloteau, JP ;

Pouzieux, S ;

Choi-Sledeski, YM ;

Becker, MR ;

Klein, SI ;

Ewing, WR ;

Pauls, HW ;

Spada, AP ;

Mikol, V .

JOURNAL OF MEDICINAL CHEMISTRY, 2000, 43 (17) :3226-3232