Completion of a programmable DNA-binding small molecule library

被引：59

作者：

Hsu, Carey F. ^{[1
]}

Phillips, John W. ^{[1
]}

Trauger, John W. ^{[1
]}

Farkas, Michelle E. ^{[1
]}

Belitsky, Jason M. ^{[1
]}

Heckel, Alexander ^{[1
]}

Olenyuk, Bogdan Z. ^{[1
]}

Puckett, James W. ^{[1
]}

Wang, Clay C. C. ^{[1
]}

Dervan, Peter B. ^{[1
]}

机构：

[1] CALTECH, Div Chem & Chem Engn, Pasadena, CA 91125 USA

来源：

TETRAHEDRON | 2007年 / 63卷 / 27期

关键词：

molecular recognition; gene regulation; polyamide; small molecule-nucleic acid interaction;

D O I：

10.1016/j.tet.2007.03.041

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

Hairpin pyrrole-imidazole (Py-Im) polyamides are programmable oligomers that bind the DNA minor groove in a sequence-specific manner with affinities comparable to those of natural DNA-binding proteins. These cell-permeable small molecules have been shown to enter the nuclei of live cells and downregulate endogenous gene expression. We complete here a library of 27 hairpin Py-Im polyamides, which bind seven-base-pair sequences of the general form 5'-WWGNNNW-3' (where W=A or T, N=W, G, or C). Their equilibrium association constants (Ka) range from K-a = 1 x 10(8) to 4 x 10(10) M-1 with good sequence specificity. A table of binding affinities and sequence contexts for this completed 27-member library has been assembled for the benefit of the chemical biology community interested in molecular control of transcription. (c) 2007 Elsevier Ltd. All rights reserved.

引用

页码：6146 / 6151

页数：6

共 53 条

[1] Small-molecule inhibitors of protein-protein interactions: Progressing towards the dream [J].

Arkin, MR ;

Wells, JA .

NATURE REVIEWS DRUG DISCOVERY, 2004, 3 (04) :301-317

[2] Solid phase synthesis of polyamides containing imidazole and pyrrole amino acids [J].

Baird, EE ;

Dervan, PB .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1996, 118 (26) :6141-6146

[3] Specific adenine alkylation by pyrrole-imidazole CBI conjugates [J].

Bando, T ;

Narita, A ;

Sasaki, S ;

Sugiyama, H .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2005, 127 (40) :13890-13895

[4] Cellular uptake of N-methylpyrrole/N-methylimidazole polyamide-dye conjugates [J].

Belitsky, JM ;

Leslie, SJ ;

Arora, PS ;

Beerman, TA ;

Dervan, PB .

BIOORGANIC & MEDICINAL CHEMISTRY, 2002, 10 (10) :3313-3318

[5]

BELITSKY JM, 2002, THESIS CALIFORNIA I

[6] Nuclear localization of pyrrole-imidazole polyamide-fluorescein conjugates in cell culture [J].

Best, TP ;

Edelson, BS ;

Nickols, NG ;

Dervan, PB .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2003, 100 (21) :12063-12068

[7] DNA sequence-specific polyamides alleviate transcription inhibition associated with long GAA•TTC repeats in Friedreich's ataxia [J].

Burnett, Ryan ;

Melander, Christian ;

Puckett, James W. ;

Son, Leslie S. ;

Wells, Robert D. ;

Dervan, Peter B. ;

Gottesfeld, Joel M. .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2006, 103 (31) :11497-11502

[8] Targeted derepression of the human immunodeficiency virus type 1 long terminal repeat by pyrrole-imidazole polyamides [J].

Coull, JJ ;

He, GC ;

Melander, C ;

Rucker, VC ;

Dervan, PB ;

Margolis, DM .

JOURNAL OF VIROLOGY, 2002, 76 (23) :12349-12354

[9] Controlling the intracellular localization of fluorescent polyamide analogues in cultured cells [J].

Crowley, KS ;

Phillion, DP ;

Woodard, SS ;

Schweitzer, BA ;

Singh, M ;

Shabany, H ;

Burnette, B ;

Hippenmeyer, P ;

Heitmeier, M ;

Bashkin, JK .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2003, 13 (09) :1565-1570

[10] Transcription factors as targets for cancer therapy [J].

Darnell, JE .

NATURE REVIEWS CANCER, 2002, 2 (10) :740-749

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