Synthesis of a non-cationic, water-soluble perylenetetracarboxylic diimide and its interactions with G-quadruplex-forming DNA

被引：61

作者：

Samudrala, Ramakrishna ^{[1
]}

Zhang, Xu ^{[1
]}

Wadkins, Randy M. ^{[1
]}

Mattern, Daniell Lewis ^{[1
]}

机构：

[1] Univ Mississippi, Dept Chem & Biochem, University, MS 38677 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2007年 / 15卷 / 01期

基金：

美国国家科学基金会;

关键词：

D O I：

10.1016/j.bmc.2006.09.075

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 number of N, N'-disubstituted perylenetetracarboxylic diimides have been reported to bind effectively to DNA that adopts G-quadruplex motifs. In some cases, this binding may actively drive the transition from single-strand DNA to the quadruplex form. The perylenediimides in the reported cases all have amine-containing side chains, which are thought to interact with the grooves of the quadruplex and help dictate the selectivity of these compounds for quadruplex versus duplex DNA. We synthesized a polyethyleneglycol-swallowtailed (PEG-tailed) perylenediimide that is water-soluble even though it is uncharged. Binding to duplex and quadruplex DNA of this perylenediimide was studied by fluorescence quenching titrations under a variety of salt conditions, and the compound's effect on quadruplex formation was studied by non-denaturing gel electrophoresis. Our results indicate that while the molecule binds to single-stranded DNA quite effectively and with selectivity, it does not drive the transition of the DNA to the tetrameric quadruplex structure, supporting the idea that charge neutralization is a key component of perylene compounds that stabilize tetrameric quadruplexes. (c) 2006 Elsevier Ltd. All rights reserved.

引用

页码：186 / 193

页数：8

共 34 条

[1] Preparation of aminoalkyl chlorohydrin hydrochlorides: Key building blocks for hydroxyethylamine-based HIV protease inhibitors [J].

Beaulieu, PL ;

Wernic, D .

JOURNAL OF ORGANIC CHEMISTRY, 1996, 61 (11) :3635-3645

[2]

Benoist E, 1998, SYNTHESIS-STUTTGART, P1113

[3] Unexpected formation of 3-substituted 1,2,3,4-tetrahydroisoquinolines during tosylation of N,N-dibenzylaminols [J].

Chandrasekhar, S ;

Mohanty, PK ;

Harikishan, K ;

Sasmal, PK .

ORGANIC LETTERS, 1999, 1 (06) :877-878

[4] Synthesis and characterization of liquid crystalline perylene diimides [J].

Cormier, RA ;

Gregg, BA .

CHEMISTRY OF MATERIALS, 1998, 10 (05) :1309-1319

[5] VERY SOLUBLE AND PHOTOSTABLE PERYLENE FLUORESCENT DYES [J].

DEMMIG, S ;

LANGHALS, H .

CHEMISCHE BERICHTE-RECUEIL, 1988, 121 (02) :225-230

[6]

Dombi KL, 2002, SYNTHESIS-STUTTGART, P816

[7]

Grand CL, 2002, MOL CANCER THER, V1, P565

[8] 4-STRANDED NUCLEIC-ACID STRUCTURES 25 YEARS LATER - FROM GUANOSINE GELS TO TELOMER DNA [J].

GUSCHLBAUER, W ;

CHANTOT, JF ;

THIELE, D .

JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS, 1990, 8 (03) :491-511

[9]

Harada H, 1996, CHEM PHARM BULL, V44, P2205

[10] Secondary DNA structures as molecular targets for cancer therapeutics [J].

Hurley, LH .

BIOCHEMICAL SOCIETY TRANSACTIONS, 2001, 29 :692-696

← 1 2 3 4 →