کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5372242 | 1388869 | 2007 | 12 صفحه PDF | دانلود رایگان |
The promoter of human telomerase reverse transcriptase (hTERT) gene, in the region from â 1000 to + 1, contains two homopurine-homopyrimidine sequences (â 835/â 814 and â 108/â 90), that can be considered as potential targets to triple helix forming oligonucleotides (TFOs) for applying antigene strategy.We have chosen the sequence (â 108/â 90) on the basis of its unfavorable chromatin organization, evaluated by theoretical nucleosome positioning and nuclease hypersensitive sites mapping. On this sequence, anti-parallel triplex with satisfactory thermodynamic stability is formed by two TFOs, having different lengths.Triplex stability is significantly increased by specific interactions with the perylene derivative N,Nâ²-bis[3,3â²-(dimethylamino) propylamine]-3,4,9,10-perylenetetracarboxylic diimide (DAPER).Since DAPER is a symmetric molecule, the induced Circular Dichroism (CD) spectra in the range 400-600 nm allows us to obtain information on drug binding to triplex and duplex DNA. The drug-induced ellipticity is significantly higher in the case of triplex with respect to duplex and, surprisingly, it increases at decreasing of DNA. A model is proposed where self-stacked DAPER binds to triplex or to duplex narrow grooves.
Journal: Biophysical Chemistry - Volume 129, Issue 1, August 2007, Pages 70-81