AzaHx, a novel fluorescent, DNA minor groove and G.C recognition element: Synthesis and DNA binding properties of a p-anisyl-4-aza-benzimidazole-pyrrole-imidazole (azaHx-PI) polyamide

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

卷:25

Article

Satam, Vijay¹  Babu, Balaji¹  Patil, Pravin¹  Brien, Kimberly A.¹  Olson, Kevin¹  Savagian, Mia¹  Lee, Megan¹  Mepham, Andrew¹  Jobe, Laura Beth²  Bingham, John P.³  Pett, Luke³  Wang, Shuo⁴  Ferrara, Maddi⁵  Bruce, Chrystal D.⁵  Wilson, W. David⁴  Lee, Moses^1,4  Hartley, John A.³  Kiakos, Konstantinos³ 

[1] Hope Coll, Dept Chem, Holland, MI 49423 USA

[2] Erskine Coll, Dept Chem, Due West, SC 29639 USA

[3] UCL Canc Inst, Canc Res UK Drug DNA Interact Res Grp, London WC1E 6BT, England

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

[5] John Carroll Univ, Dept Chem, University Hts, OH 44118 USA

关键词: AzaHx;    Hx-amides;    DNA;    Sequence recognition;    Minor groove;    Distamycin;    Polyamides;    Hoechst 33258;   

DOI  :  10.1016/j.bmcl.2015.06.055

来源: Elsevier

【 摘 要 】

The design, synthesis, and DNA binding properties of azaHx-PI or p-anisyl-4-aza-benzimidazole-pyrrole-imidazole (5) are described. AzaHx, 2-(p-anisyl)-4-aza-benzimidazole-5-carboxamide, is a novel, fluorescent DNA recognition element, derived from Hoechst 33258 to recognize G.C base pairs. Supported by theoretical data, the results from DNase I footprinting, CD, Delta T-M, and SPR studies provided evidence that an azaHx/IP pairing, formed from antiparallel stacking of two azaHx-PI molecules in a side-by-side manner in the minor groove, selectively recognized a C-G doublet. AzaHx-PI was found to target 5'-ACGCGT-3', the Mlu1 Cell Cycle Box (MCB) promoter sequence with specificity and significant affinity (K-eq 4.0 +/- 0.2 x 10(7) M (1)). (C) 2015 Elsevier Ltd. All rights reserved.

【 授权许可】

Free