tailieunhanh - Báo cáo khoa học: Binding of berberine to human telomeric quadruplex – spectroscopic, calorimetric and molecular modeling studies

This study examines the characteristics of binding of berberine to the human telomeric d[AG3(T2AG3 )3] quadruplex. By employing UV-visible spectroscopy, fluorescence spectroscopy and isothermal titration calorime-try, we found that the binding affinity of berberine to the human telomeric quadruplex is 10 6 . | ỊFEBS Journal Binding of berberine to human telomeric quadruplex - spectroscopic calorimetric and molecular modeling studies Amit Arora1 Chandramouli Balasubramanian1 Niti Kumar1 Saurabh Agrawal1 Rajendra P. Ojha2 and Souvik Maiti1 1 Proteomics and StructuralBiology Unit Institute of Genomics and Integrative Biology CSIR Delhi India 2 Biophysics Unit Department of Physics DDU Gorakhpur University India Keywords berberine hydration quadruple quadruplex-ligand interaction thermodynamics 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 11 April2008 revised 16 May 2008 accepted 9 June 2008 doi This study examines the characteristics of binding of berberine to the human telomeric d AG3 T2AG3 3 quadruplex. By employing UV-visible spectroscopy fluorescence spectroscopy and isothermal titration calorimetry we found that the binding affinity of berberine to the human telomeric quadruplex is 106. The complete thermodynamic profile for berberine binding to the quadruplex at 25 C shows a small negative enthalpy AH of kcal-mol-1 an entropy change with TAS of kcal-mol-1 and an overall favorable free energy AG of kcal-mol-1 .Through the temperature dependence of AH we obtained a heat capacity ACp of -94 5 cal-mol-1-K-1. The osmotic stress method revealed that there is an uptake of 13 water molecules in the complex relative to the free reactants. Furthermore the molecular modeling studies on different quadruplex-berberine complexes show that berberine stacking at the external G-quartet is mainly aided by the p-p interaction and the stabilization of the high negative charge density of O6 of guanines by the positively charged N7 of berberine. The theoretical heat capacity ACp values for quadruplex-berberine models are -89 and -156 cal-mol-1-K-1. The telomere is a region .