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AbstractBinding interactions of the phenazinium dye Janus green blue (JGB) with human and bovine serum albumins (BSA – and BSA) have been explored for the first time from multi-spectroscopic and calorimetric measurements aided by in silicocalculations. The formation of ground state complexes between JGB and the respective serum albumins have been suggested from the UV–Vis and steady-state fluorescence spectroscopic studies. The nonlinear Stern Volmer (SV) plots at higher concentrations of JGB primarily indicate the formation of more than one ground state complexes in BSA –/BSA–JGB systems. Modified SV plots and isothermal titration calorimetry (ITC) studies however signify the possibilities of one type of binding complexes between HSA/BSA – JGB systems. Binding constants and the thermodynamic parameters associated with the HSA/BSA–JGB complexes have also been estimated from the ITC studies. Förster distances (R0) for HSA–JGB and BSA–JGB complexes are estimated from Förster resonance energy transfer (FRET) results. Variations in the micro-environment of the Tyr and Trp residues of the serum proteins in presence of JGB have been observed from the synchronous fluorescence measurements. The conformational changes in the protein structures induced by the dye JGB have been revealed from 3 D fluorescence and circular dichroism (CD) studies. The experimental observations are supported by in silicocalculations. This in depth investigation on the interactions of serum albumins with JGB may provide the fundamental information toward exploring the therapeutic efficacy of JGB as a potent drug molecule. Communicated by Ramaswamy H. Sarma

AbstractBinding interaction between the small antitumor drug Hydroxyurea (HU) and Bovine Hemoglobin (BHb) has been explored in details from multi-spectroscopic and computational studies. The formation of ground state complex between BHb and HU has been suggested from the electronic UV–Vis and steady-state fluorescence spectroscopic studies. The quenching in fluorescence of BHb in presence of HU at varied concentrations has been analyzed from the SV plots. Static type of quenching has been suggested from time-resolved fluorescence spectroscopic studies. Binding parameters associated with the BHb-HU complex have also been estimated from the temperature dependent fluorescence spectroscopic studies. Alterations in the micro-environment of the Tyr and Trp residues of BHb in presence of HU have been observed from the synchronous fluorescence measurement. The result obtained from CD spectroscopic measurements signify partial unfolding in the secondary structure of BHb due to binding with HU molecule. The experimental observations are supported by theoretical studies. Molecular docking and molecular dynamics simulations have been performed to investigate the structural stability and compactness of BHb in the binding interaction between BHb and HU. The interaction of BHb with HU is expected to provide fundamental insights towards understanding the therapeutic effectiveness of HU upon interaction with BHb used in chemo-, radio therpeutic procedures and also in the treatment of SCD.

This article describes how a natural alkaloid allocryptopine (ALL) is able to differentiate two forms of biologically relevant human telomeric (htel22) G-quadruplex DNAs (GQ-DNA) depending on the presence of K+and Na+ions by steady-state and time-resolved spectroscopic techniques. For both interactions, predominant involvements of static-type quenching mechanism with the negligible influence of dynamic collision are established by UV–vis absorption and fluorescence emission study, which is further supported by fluorescence lifetime measurements. ALL exhibits appreciable affinity toward both GQ-DNAs. Both the mixed-hybrid (3 + 1) quadruplex structures in K+ions and the basket-type antiparallel quadruplex structure under Na+condition are converted to parallel types in the presence of ALL. Fluorescence intercalator displacement assay experiment revealed modest selectivity of ALL to both quadruplexes over duplex DNA along with higher selectivity for antiparallel types among the two quadruplexes via groove and/or loop binding, which is distinct from the conventional π-stacking of the ligands on external G-quartets. ALL stabilized both GQ-DNA topologies moderately. The differences in the dynamics of ALL within both DNA environments have been demonstrated vividly by time-resolved anisotropy measurements using the wobbling-in-cone model. These results suggest groove binding with antiparallel G-quartet with high affinity and moderate loop binding with mixed-hybrid G-quartet accompanied by the partial end stacking additionally in both of the cases. Our conclusions are further supported by steady-state anisotropy measurements and molecular docking. The present investigation can be used in the development of a biocompatible antitumour/anticancer agent targeting particular GQ-DNA conformation.