کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10586560 | 981393 | 2010 | 9 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Targeting the ICB2 site of the topoisomerase IIα promoter with a formamido-pyrrole-imidazole-pyrrole H-pin polyamide
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کلمات کلیدی
موضوعات مرتبط
مهندسی و علوم پایه
شیمی
شیمی آلی
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چکیده انگلیسی
The synthesis, DNA binding characteristics and biological activity of an N-formamido pyrrole- and imidazole-containing H-pin polyamide (f-PIP H-pin, 2) designed to selectively target the ICB2 site on the topoIIα promoter, is reported herein. Thermal denaturation, circular dichroism, isothermal titration calorimetry, surface plasmon resonance and DNase I footprinting studies demonstrated that 2 maintained the selectivity of the unlinked parent monomer f-PIP (1) and with a slight enhancement in binding affinity (Keq = 5 Ã 105 Mâ1) to the cognate site (5â²-TACGAT-3â²). H-pin 2 also exhibited comparable ability to inhibit NF-Y binding to 1, as demonstrated by gel shift studies. However, in stark contrast to monomer 1, the H-pin did not affect the up-regulation of topoisomerase IIα (topoIIα) in cells (Western blot), suggesting that the H-pin does not enter the nucleus. This study is the first to the authors' knowledge that reports such a markedly different cellular response between two compounds of almost identical binding characteristics.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bioorganic & Medicinal Chemistry - Volume 18, Issue 15, 1 August 2010, Pages 5553-5561
Journal: Bioorganic & Medicinal Chemistry - Volume 18, Issue 15, 1 August 2010, Pages 5553-5561
نویسندگان
Andrew Franks, Christopher Tronrud, Konstantinos Kiakos, Jerome Kluza, Manoj Munde, Toni Brown, Hilary Mackay, W. David Wilson, Daniel Hochhauser, John A. Hartley, Moses Lee,