Mixed up minor groove binders: Convincing A.T specific compounds to recognize a G.C base pair

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

卷:25

Article

Paul, Ananya^1,2  Nanjunda, Rupesh^1,2  Kumar, Arvind^1,2  Laughlin, Sarah^1,2  Nhili, Raja^3,4  Depauw, Sabine^3,4  Deuser, Shelby Sheldon^1,2  Chai, Yun^1,2  Chaudhary, Arpana S.^1,2  David-Cordonnier, Marie-Helene^3,4  Boykin, David W.^1,2  Wilson, W. David^1,2 

[1] Georgia State Univ, Dept Chem, Atlanta, GA 30303 USA

[2] Georgia State Univ, Ctr Diagnost & Therapeut, Atlanta, GA 30303 USA

[3] Univ Lille, INSERM, UMR S1172, JPARC, F-59045 Lille, France

[4] Ctr Hosp Lille, Inst Rech Canc Lille, F-59045 Lille, France

关键词: Sequence specificity;    Mixed DNA recognition;    Rational design;    Heterocyclic diamidines;    Biophysical analysis;   

DOI  :  10.1016/j.bmcl.2015.05.005

来源: Elsevier

【 摘 要 】

DNA minor-groove-binding compounds have limited biological applications, in part due to problems with sequence specificity that cause off-target effects. A model to enhance specificity has been developed with the goal of preparing compounds that bind to two AT sites separated by G.C base pairs. Compounds of interest were probed using thermal melting, circular dichroism, mass spectrometry, biosensor-SPR, and molecular modeling methods. A new minor groove binder that can strongly and specifically recognize a single G.C base pair with flanking AT sequences has been prepared. This multi-site DNA recognition mode offers novel design principles to recognize entirely new DNA motifs. (C) 2015 Elsevier Ltd. All rights reserved.

【 授权许可】

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