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

作者：Satam Vijay; Babu Balaji; Patil Pravin; Brien Kimberly A; Olson Kevin; Savagian Mia; Lee Megan; Mepham Andrew; Jobe Laura Beth; Bingham John P; Pett Luke; Wang Shuo; Ferrara Maddi; Bruce Chrystal D; Wilson W David; Lee Moses; Hartley John A; Kiakos Konstantinos

来源：Bioorganic & Medicinal Chemistry Letters, 2015, 25(17): 3681-3685.

DOI：10.1016/j.bmcl.2015.06.055

• AzaHx
• Hx-amides
• DNA
• Sequence recognition
• Minor groove
• Distamycin
• Polyamides
• Hoechst 33258

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)).

• 出版日期2015-9-1