Synthesis and DNA Binding Properties of 1-(3-aminopropyl)-imidazole-containing Triamide f-Im*PyIm: A Novel Diamino Polyamide Designed to Target 5 '-ACGCGT-3 '

Document Type

Article

Publication Date

9-15-2012

Publication Source

Bioorganic & Medicinal Chemistry Letters

Volume Number

22

Issue Number

18

First Page

5898

Last Page

5902

Publisher

Pergamon-Elsevier Science Ltd.

ISSN

0960-894X

Abstract

A novel diamino/dicationic polyamide f-Im*PyIm (5) that contains an orthogonally positioned aminopropyl chain on an imidazole (Im*) moiety was designed to target 5'-ACGCGT-3'. The DNA binding properties of the diamino polyamide 5, determined by CD, Delta T-M, DNase I footprinting, SPR, and ITC studies, were compared with those of its monoamino/monocationic counterpart f-ImPyIm (1) and its diamino/dicationic isomer f-ImPy*Im (2), which has the aminopropyl group attached to the central pyrrole unit (Py*). The results gave evidence for the minor groove binding and selectivity of polyamide 5 for the cognate sequence 5'-ACGCGT-3', and with strong affinity (K-eq = 2.3 x 10(7) M-1). However, the binding affinities varied according to the order: f-ImPy*Im (2) > f-ImPyIm (1) >= f-Im*PyIm (5) confirming that the second amino group can improve affinity, but its position within the polyamide can affect affinity. (C) 2012 Elsevier Ltd. All rights reserved.

Keywords

PYRROLE-IMIDAZOLE POLYAMIDES, CELL-CYCLE BOX, MINOR-GROOVE, MOLECULAR RECOGNITION, NUCLEAR-LOCALIZATION, GENE-EXPRESSION, SEQUENCE RECOGNITION, DISTAMYCIN-A, TRANSCRIPTION, MODULATION

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