tailieunhanh - Báo cáo khoa học: Effect of flanking bases on quadruplex stability and Watson–Crick duplex competition

Guanine-rich DNA sequences have the ability to fold into four-stranded structures called G-quadruplexes, and are considered as promising antican-cer targets. Although the G-quadruplex structure is composed of quartets and interspersed loops, in the genome it is also flanked on each side by numerous bases. | Effect of flanking bases on quadruplex stability and Watson-Crick duplex competition Amit Arora Divya R. Nair and Souvik Maiti Proteomics and StructuralBiology Unit Institute of Genomics and Integrative Biology Councilfor Scientific and IndustrialResearch CSIR MallRoad Delhi India Keywords c-kit equilibrium flank length quadruple Watson-Crick duplex Correspondence S. Maiti Proteomics and StructuralBiology Unit Institute of Genomics and Integrative Biology CSIR MallRoad Delhi 110 007 India Fax 91 11 2766 7471 Tel 91 11 2766 6156 E-mail souvik@ Received 8 February 2009 revised 5 April 2009 accepted 1 May 2009 doi Guanine-rich DNA sequences have the ability to fold into four-stranded structures called G-quadruplexes and are considered as promising anticancer targets. Although the G-quadruplex structure is composed of quartets and interspersed loops in the genome it is also flanked on each side by numerous bases. The effect of loop length and composition on quadruplex conformation and stability has been well investigated in the past but the effect of flanking bases on quadruplex stability and Watson-Crick duplex competition has not been addressed. We have studied in detail the effect of flanking bases on quadruplex stability and on duplex formation by the G-quadruplex in the presence of complementary strands using the quadru-plex-forming sequence located in the promoter region of the c-kit oncogene. The results obtained from CD thermal difference spectrum and UV melting demonstrated the effect of flanking bases on quadruplex structure and stability. With the increase in flank length the increase in the more favorable DHvH is accompanied by a striking increase in the unfavorable DSvH which resulted in a decrease in the overall DGvH of quadruplex formation. Furthermore CD fluorescence and isothermal titration calorimetry studies demonstrated that the propensity to attain quadruplex structure decreases with increasing flank .

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