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 '
Bioorganic & Medicinal Chemistry Letters
Pergamon-Elsevier Science Ltd.
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.
PYRROLE-IMIDAZOLE POLYAMIDES, CELL-CYCLE BOX, MINOR-GROOVE, MOLECULAR RECOGNITION, NUCLEAR-LOCALIZATION, GENE-EXPRESSION, SEQUENCE RECOGNITION, DISTAMYCIN-A, TRANSCRIPTION, MODULATION
Satam, Vijay, Balaji Babu, Alexander Porte, Mia Savagian, Megan Lee, Thomas Smeltzer, Yang Liu, W. David Wilson, Shicai Lin, Kostantinos Kiakos, John A. Hartley and Moses Lee. "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 '." Bioorganic & Medicinal Chemistry Letters 22, no. 18 (2012): 5898-5902.