Targeting G-quadruplexes in gene promoters: a novel anticancer strategy?

被引：1412

作者：

Balasubramanian, Shankar ^{[1
,2
,3
]}

Hurley, Laurence H. ^{[4
,5
,6
]}

Neidle, Stephen ^{[7
,8
]}

机构：

[1] Univ Cambridge, Dept Chem, Cambridge CB2 1EW, England

[2] Canc Res UK, Cambridge Res Inst, Li Ka Shing Ctr, Cambridge CB2 0RE, England

[3] Univ Cambridge, Sch Clin Med, Cambridge CB2 0SP, England

[4] Univ Arizona, Coll Pharm, Tucson, AZ 85721 USA

[5] Univ Arizona, Inst BIO5, Tucson, AZ 85721 USA

[6] Univ Arizona, Arizona Canc Ctr, Tucson, AZ 85724 USA

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

[8] Univ London, Sch Pharm, Ctr Canc Med, London WC1N 1AX, England

来源：

NATURE REVIEWS DRUG DISCOVERY | 2011年 / 10卷 / 04期

基金：

美国国家卫生研究院; 英国生物技术与生命科学研究理事会;

关键词：

C-MYC PROMOTER; NUCLEASE HYPERSENSITIVE ELEMENT; REPLICATION PROTEIN-A; NUCLEOSIDE DIPHOSPHATE KINASE; TELOMERIC G-QUADRUPLEXES; GENOME-WIDE ANALYSIS; HUMAN KRAS PROMOTER; I-MOTIF STRUCTURES; SMALL-MOLECULE; INTERACTIVE AGENT;

D O I：

10.1038/nrd3428

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 ; 0836 ; 090102 ; 100705 ;

摘要：

G-quadruplexes are four-stranded DNA structures that are over-represented in gene promoter regions and are viewed as emerging therapeutic targets in oncology, as transcriptional repression of oncogenes through stabilization of these structures could be a novel anticancer strategy. Many gene promoter G-quadruplexes have physicochemical properties and structural characteristics that might make them druggable, and their structural diversity suggests that a high degree of selectivity might be possible. Here, we describe the evidence for G-quadruplexes in gene promoters and discuss their potential as therapeutic targets, as well as progress in the development of strategies to harness this potential through intervention with small-molecule ligands.

引用

页码：261 / 275

页数：15

共 143 条

[1] Solution structure of the biologically relevant g-quadruplex element in the human c-MYC promoter. implications for g-quadruplex stabilization [J].