Title

Hx-amides: DNA Sequence Recognition by the Fluorescent Hx (p-anisylbenzimidazole)•Pyrrole and Hx•Imidazole Pairings

Document Type

Article

Publication Date

3-15-2013

Publication Source

Bioorganic & Medicinal Chemistry Letters

Volume Number

23

Issue Number

6

First Page

1699

Last Page

1702

Publisher

Pergamon-Elsevier Science Ltd.

ISSN

0960-894X

Abstract

Hx-amides are fluorescent hybrids of imidazole (1)- and pyrrole (P)-containing polyamides and Hoechst 33258, and they bind in the minor groove of specific DNA sequences. Synthesis and DNA binding studies of HxII (5) complete our studies on the first set of Hx-amides: Hx-I/P-I/P. HxPP (2), HxIP (3) and HxPI (4) were reported earlier. Results from DNase I footprinting, biosensor-SPR, CD and Delta T-M studies showed that Hx-amides interacted with DNA via the anti-parallel and stacked, side-by-side motif. Hx was found to mimic the DNA recognition properties of two consecutive pyrrole units (PP) in polyamides. Accordingly, the stacked Hx/PP pairing binds preferentially to two consecutive AT base pairs, A/T-A/T; Hx/IP prefers C-A/T; Hx/PI prefers A/T-C; and Hx/II prefers C-C. The results also showed that Hx-amides bound their cognate sequence at a higher affinity than their formamido-triamide counterparts. (C) 2013 Elsevier Ltd. All rights reserved.

Keywords

Hx-amides; DNA; Sequence recognition; Minor groove; Distamycin; Hoechst 33258 KeyWords Plus: MINOR-GROOVE; MOLECULAR RECOGNITION; NUCLEAR-LOCALIZATION; BINDING-AFFINITY; POLYAMIDES; SPECIFICITY; NMR; OLIGOPEPTIDES; PERMEABILITY; NETROPSIN

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