Selectivity in Ligand Recognition of G-Quadruplex Loops

被引：108

作者：

Campbell, Nancy H. ^{[1
]}

Patel, Manisha ^{[1
]}

Tofa, Amina B. ^{[1
]}

Ghosh, Ragina ^{[1
]}

Parkinson, Gary N. ^{[1
]}

Neidle, Stephen ^{[1
]}

机构：

[1] Univ London, Sch Pharm, Canc Res UK Biomol Struct Grp, London WC1N 1AX, England

来源：

BIOCHEMISTRY | 2009年 / 48卷 / 08期

关键词：

TELOMERIC G-QUADRUPLEX; PROXIMAL PROMOTER; CRYSTAL-STRUCTURE; DRUG RECOGNITION; STRUCTURAL BASIS; SMALL-MOLECULE; DNA; SEQUENCE; TOPOLOGY; STABILITY;

D O I：

10.1021/bi802233v

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 series of disubstituted acridine ligands have been cocrystallized with a bimolecular DNA G-quadruplex. The ligands have a range of cyclic amino end groups of varying size. The crystal structures show that the diagonal loop in this quadruplex results in a large cavity for these groups, in contrast to the steric constraints imposed by propeller loops in human telomeric quadruplexes. We conclude that the nature of the loop has a significant influence on ligand selectivity for particular quadruplex folds.

引用

页码：1675 / 1680

页数：6

共 45 条

[21] Drug targeting of the c-MYC promoter to repress gene expression via a G-quadruplex silencer element [J].

Hurley, Laurence H. ;

Von Hoff, Daniel D. ;

Siddiqui-Jain, Adam ;

Yang, Danzhou .

SEMINARS IN ONCOLOGY, 2006, 33 (04) :498-512

[22] A hitchhiker's guide to G-quadruplex ligands [J].

Monchaud, David ;

Teulade-Fichou, Marie-Paule .

ORGANIC & BIOMOLECULAR CHEMISTRY, 2008, 6 (04) :627-636

[23] Trisubstituted acridines as G-quadruplex telomere targeting agents. Effects of extensions of the 3,6-and 9-side chains on quadruplex binding, telomerase activity, and cell proliferation [J].

Moore, MJB ;

Schultes, CM ;

Cuesta, J ;

Cuenca, F ;

Gunaratnam, M ;

Tanious, FA ;

Wilson, WD ;

Neidle, S .

JOURNAL OF MEDICINAL CHEMISTRY, 2006, 49 (02) :582-599

[24] Refinement of macromolecular structures by the maximum-likelihood method [J].

Murshudov, GN ;

Vagin, AA ;

Dodson, EJ .

ACTA CRYSTALLOGRAPHICA SECTION D-STRUCTURAL BIOLOGY, 1997, 53 :240-255

[25] Physiological relevance of telomeric G-quadruplex formation: a potential drug target [J].

Oganesian, Liana ;

Bryan, Tracy M. .

BIOESSAYS, 2007, 29 (02) :155-165

[26] G-quadruplexes: Targets in anticancer drug design [J].

Ou, Tian-miao ;

Lu, Yu-jing ;

Tan, Jia-heng ;

Huang, Zhi-shu ;

Wong, Kwok-Yin ;

Gu, Lian-quan .

CHEMMEDCHEM, 2008, 3 (05) :690-713

[27] Topology conservation and loop flexibility in quadruplex-drug recognition: Crystal structures of inter- and intramolecular telomeric DNA quadruplex-drug complexes [J].

Parkinson, Gary N. ;

Cuenca, Francisco ;

Neidle, Stephen .

JOURNAL OF MOLECULAR BIOLOGY, 2008, 381 (05) :1145-1156

[28] Structural basis for binding of porphyrin to human telomeres [J].

Parkinson, Gary N. ;

Ghosh, Ragini ;

Neidle, Stephen .

BIOCHEMISTRY, 2007, 46 (09) :2390-2397

[29] Crystal structure of parallel quadruplexes from human telomeric DNA [J].

Parkinson, GN ;

Lee, MPH ;

Neidle, S .

NATURE, 2002, 417 (6891) :876-880

[30] Human telomere, oncogenic promoter and 5'-UTR G-quadruplexes: Diverse higher order DNA and RNA targets for cancer therapeutics [J].

Patel, Dinshaw J. ;

Phan, Anh Tuan ;

Kuryavyi, Vitaly .

NUCLEIC ACIDS RESEARCH, 2007, 35 (22) :7429-7455

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