Completion of a Programmable DNA-Binding Small Molecule Library

Overview

Journal Tetrahedron

Specialty Chemistry

Date 2008 Jul 4

PMID 18596841

Citations 43

Authors

Carey F Hsu

John W Phillips

John W Trauger

Michelle E Farkas

Jason M Belitsky

Alexander Heckel

Bogdan Z Olenyuk

James W Puckett

Clay C C Wang

Peter B Dervan

Affiliations

Soon will be listed here.

Abstract

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 7-base-pair sequences of the general form 5'-WWGNNNW-3' (where W = A or T, N = W, G, or C). Their equilibrium association constants (K(a)) range from K(a) = 1×10(8) M(-1) to 4×10(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.

Citing Articles

Potentiometric Determination of Acid Dissociation Constants (p ) for an Anticancer Pyrrole-Imidazole Polyamide.

Li X, Shi Z, Jia T ACS Med Chem Lett. 2022; 13(11):1739-1744.

PMID: 36385938 PMC: 9661695. DOI: 10.1021/acsmedchemlett.2c00348.

Single position substitution of hairpin pyrrole-imidazole polyamides imparts distinct DNA-binding profiles across the human genome.

Finn P, Bhimsaria D, Ali A, Eguchi A, Ansari A, Dervan P PLoS One. 2020; 15(12):e0243905.

PMID: 33351840 PMC: 7755219. DOI: 10.1371/journal.pone.0243905.

Modulating DNA by polyamides to regulate transcription factor PU.1-DNA binding interactions.

Liu B, Bashkin J, Poon G, Wang S, Wang S, Wilson W Biochimie. 2019; 167:1-11.

PMID: 31445072 PMC: 6883780. DOI: 10.1016/j.biochi.2019.08.009.

Sequence specific suppression of androgen receptor-DNA binding in vivo by a Py-Im polyamide.

Kurmis A, Dervan P Nucleic Acids Res. 2019; 47(8):3828-3835.

PMID: 30838415 PMC: 6486638. DOI: 10.1093/nar/gkz153.

Molecules targeting the androgen receptor (AR) signaling axis beyond the AR-Ligand binding domain.

Elshan N, Rettig M, Jung M Med Res Rev. 2018; 39(3):910-960.

PMID: 30565725 PMC: 6608750. DOI: 10.1002/med.21548.

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