Multi-spectroscopic studies of the interaction of new synthesized platin complex with human carrier protein of serum albumin.

Previous reports have shown that protein-drug interaction helps to improve the pharmacokinetics of the drugs. Human serum albumin (HSA) is one of the basic components of blood plasma and it serves as a storage and carrier protein. In the present study, the interaction of a new synthesized Pt [iso]2 complex (cis - [Pt(NH2-Isopentylamine)2(Isopentylglycine)]NO3) with HSA was studied using the spectroscopic methods of fluorescence and circular dichroic (CD) at two different temperatures of 25 and 37 °C. Analysis of the quenching mechanism via Stern-Volmer curve, determination of HSA binding parameters (0.65 × 104 and 2.27 × 104) and standard Gibbs free energy (-25.8, and 21.77) at 25 and 37 °C, respectively, carried out using fluorescence quenching data. Data analysis showed that the static mechanism has the main role in fluorescence quenching. Also, the number of protein binding sites for complex indicated one binding site at two temperatures of 25 and 37 °C. The secondary structure of protein in the presence of different concentrations of Pt(II) complex did not show any significant alterations. Whereas, thermal stability of the HSA was reduced in the presence of complex. Also, thermal analysis obtained the values of ΔG°25 for HSA and HSA in presence of Pt [Iso]2 20, 13, respectively. According to the above results, we concluded that the new synthesized Pt complex can bind to the blood carrier protein of HSA and change the stability of it which can be considered in the design of new drugs.Communicated by Ramaswamy H. Sarma.

Mechanism of the interaction of plant alkaloid vincristine with DNA and chromatin: spectroscopic study.

Chromatin has been successfully used as a tool for the study of genome function in cancers. Vincristine as a vinca alkaloid anticancer drug exerts its action by binding to tubulins. In this study the effect of vincristine on DNA and chromatin was investigated employing various spectroscopy techniques as well as thermal denaturation, equilibrium dialysis and DNA-cellulose affinity. The results showed that the binding of vincristine to DNA and chromatin reduced absorbance at both 260 and 210 nm with different extent. Chromopheres of chromatin quenched with the drug and fluorescence emission intensity decreased in a dose-dependent manner. Chromatin exhibited higher emission intensity changes compared to DNA. Upon addition of vincristine, Tm of DNA and chromatin exhibited hypochromicity without any shift in Tm. The binding of the drug induced structural changes in both positive and negative extremes of circular dichroism spectra and exhibited a cooperative binding pattern as illustrated by a positive slope observed in low r values of the binding isotherm. Vincristine showed higher binding affinity to double stranded DNA compared to single stranded one. The results suggest that vincristine binds with higher affinity to chromatin compared to DNA. The interaction is through intercalation along with binding to phosphate sugar backbone and histone proteins play fundamental role in this process. The binding of the drug to chromatin opens a new insight into vincristine action in the cell nucleus.