title: Binding of berberine to human telomeric quadruplex - spectroscopic, calorimetric and molecular modeling studies.
abstract: This study examines the characteristics of binding of berberine to the human telomeric d[AG(3)(T(2)AG(3))(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 10(6). The complete thermodynamic profile for berberine binding to the quadruplex, at 25 degrees C, shows a small negative enthalpy (DeltaH) of -1.7 kcal.mol(-1), an entropy change with TDeltaS of +6.5 kcal.mol(-1), and an overall favorable free energy (DeltaG) of -8.2 kcal.mol(-1) . Through the temperature dependence of DeltaH, we obtained a heat capacity (DeltaC(p)) 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 pi-pi 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 (DeltaC(p)) values for quadruplex-berberine models are -89 and -156 cal.mol(-1).K(-1).
authors.affiliation: Proteomics and Structural Biology Unit, Institute of Genomics and Integrative Biology, CSIR, Delhi, India.
authors.forename: Amit
authors.initials: A
authors.lastname: Arora
authors.forename: Chandramouli
authors.initials: C
authors.lastname: Balasubramanian
authors.forename: Niti
authors.initials: N
authors.lastname: Kumar
authors.forename: Saurabh
authors.initials: S
authors.lastname: Agrawal
authors.forename: Rajendra P
authors.initials: RP
authors.lastname: Ojha
authors.forename: Souvik
authors.initials: S
authors.lastname: Maiti
mesh_terms: D001599:Berberine / Q000737:chemistry / Q000378:metabolism*; D002151:Calorimetry / Q000379:methods*; D008958:Models, Molecular; D013057:Spectrum Analysis / Q000379:methods*; D016615:Telomere; D013816:Thermodynamics
chemical_list: D001599:Berberine