Unraveling the binding interactions between two Pt(II) complexes of aliphatic glycine derivatives with human serum albumin: A comprehensive computational and multi-spectral investigation.

This article delves into the interaction between HSA protein and synthesized platinum complexes, with formula: [Pt(Propyl-NH2)2(Propylglycine)]NO3 and [Pt(Tertpentyl-NH2)2(Tertpentylglycine)]NO3, through a range of methods, including spectroscopic (UV-visible, fluorescence, synchronous fluorescence and CD) analysis and computational modeling (molecular docking and MD simulation). The binding constants, the number of binding sites, and thermodynamic parameters were obtained at 25 to 37 °C. The study found that both complexes could bind with HSA (moderate affinity for Tertpentyl and strong affinity for Propyl derivatives) and occupied one binding site in HSA (validated with, Stern-Volmer, Job-plots, and molecular docking investigations) located in subdomain IIA. The binding mechanisms of both mentioned Pt(II) agents were different, with the Propyl derivative predominantly using van der Waals forces and hydrogen bond interactions with a static quenching mechanism and the Tertpentyl derivative mainly utilizing hydrophobic force with a dynamic quenching mechanism. However, the two ligands affected protein differently; the Tertpentyl complex did not significantly alter the protein structure upon binding, as evidenced by synchronous fluorescence spectroscopy (SFS), CD spectroscopy, and MD analysis. The outcome helps in understanding the binding mechanisms and structural modifications induced by the ligands, which could aid in the innovation of more effective and stable Pt(II)-based drugs.

Molecular insights into the interaction of 5-fluorouracil and Fe3O4 nanoparticles with beta-casein: An experimental and theoretical study.

We investigated the potential carrier of milk beta-casein (ß-CN) and its interactions with 5-fluorouracil (5-FU) and iron oxide nanoparticles (Fe3O4 NPs). We used different spectroscopic methods of fluorescence, UV-Visble, circular dichroism (CD), synchronous fluorescence, zeta potential assay, and computational studies to clarify the protein interaction with 5-FU and Fe3O4 NPs. The fluorescence data indicated both Fe3O4 NPs and 5-FU could quench the intrinsic fluorescence of ß-CN. Fluorescence measurements showed that the single interaction of ß-CN with 5-FU or Fe3O4 NPs was static, while reacted ß-CN with both 5-FU and Fe3O4 NPs simultaneously showed a dynamic quenching. Synchronous fluorescence data in both tests revealed that the tryptophan (Trp) residue of ß-CN had a dominant role in quenching and the polarity of its microenvironment more than tyrosine (Tyr) increased in interaction with 5-FU. All the binding sites and thermodynamic parameters were obtained at 25, 37, and 42 °C. The analysis of thermodynamic parameters and Job's plot techniques pointed to that both of these complexes with the 1:1 M ratio were exothermic (ΔH°<0) driven with the van der Waals and H-bonding interactions (in agreement with the docking results). The CD spectra in the region of far-UV and thermal denaturation study indicated minor changes in the secondary structure of ß-CN in the presence of various concentrations of Fe3O4 NPs and 5-FU. Also, from the molecular dynamics (MD) analysis, as a result, the protein structure was stable during 100 ns. The outcomes highlighted that ß-CN protein could form a great bind with 5-FU and Fe3O4 NPs ligands (supporting the zeta potential assay results) by independent binding sites. These results would be helpful insight to construct a potential magnetic nanocarrier ß-CN base for 5-FU drug delivery.

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.

Probing the interaction of two chemotherapeutic drugs of oxali-palladium and 5-fluorouracil simultaneously with milk carrier protein of ß-lactoglobulin.

ß-Lactoglobulin (ßLG) is a basic element of globular carrier protein, which is the major protein in the whey of ruminant milk and is of main interest in the dairy industry. In the present study, the simultaneous effects of both of the important anticancer drugs of 5-fluorouracil (5-FU) and oxali-palladium, on the structure of ßLG were investigated using different spectroscopic methods of fluorescence and circular dichroism (CD) in combination with a molecular docking at two temperatures of 25 and 37°C. The resulted data from intrinsic fluorescence spectra of protein indicated that 5-FU and oxalli-palladium can quench the fluorescence intensity of ßLG in dose-dependent manner via static mechanism of fluorescence quenching. Analysis of fluorescence quenching data in agreement with theoretical results have represented that there are I binding sites on ßLG for binding of oxali-palladium and also II binding sites for 5-FU, at both temperatures of 25 and 37°C. Also, competitive binding results showed that the number of binding sites on protein for each of the drug when the protein incubated with one of the drug did not show any changes. The values of thermodynamic parameters of ΔH°, ΔS° and ΔG° illustrate that van der Waals and hydrogen-bond interactions have the main role in the binding of oxali-palladium and 5-FU to ßLG, respectively. The analysis of circular dichroism spectra indicated reduction in stability of the protein and alteration in the secondary structure of protein with reduction of α-helical structure and increasing of ß-sheet structure in the presence of increasing concentration of oxali-palladium and 5-FU. Also, the transition temperature (Tm) value of ßLG indicated the significant decreasing in the presence of 5-FU and oxali-palladium. As a result, it can be concluded that both of the chemotherapeutic drugs of oxali-palladium and 5-FU can bind to independent binding sites on carrier protein of ßLG, which can be used in design and simultaneous delivery of both drugs.