![]() The microenvironment of each site was described using molecular docking and the stability of the complex was verified by means of molecular dynamics. In addition, using fluorescence spectroscopy, the number of sites accessed by PPL was determined through interaction density function (IDF) method. The importance of applying the inner filter correction in all the wavelengths of the spectrum is also discussed. Here, two different data analyses were used to treat fluorescence spectra: the most common approach based on the intensity of the fluorescence signal at one specific wavelength and another based on the areas below the fluorescence spectra. The thermodynamic of the interaction between RSA and PPL is disclosed based on fluorescence spectroscopy analyses. Two approach lines of the molecular biophysical field were applied, one experimental another computational. The goal of present investigation is to elucidate the molecular biophysical mechanisms of the interaction between RSA and PPL. These proteins share the same number of disulfide bridges (17) and a Cys34 thiol group 11. S1), and high preservation of its tertiary structure (Fig. The comparison presents that RSA has 73% of sequence similarity (Fig. Therefore, based on the modeled RSA, it can be compared with the HSA structure deposited in PDB (1AO6) and several similarities can be found between them. However, RSA modeling has been performed and published in a recent article 10. The crystallographic structure of RSA has not yet been determined. RSA has 584 amino acids with just one tryptophan residue 8, which enables the use of fluorescence spectroscopy 9. Nevertheless, no information about the interaction between PPL and rat serum albumin (RSA) is known. A few works present in the literature bring the first results of the interaction of PPL with human albumin 6, 7. Considering the lipophilic characteristics of PPL, its transport through plasma must be assisted by carrier proteins, such as albumin. Published pharmacokinetic studies report that oral, intravenous and intraperitoneal administration in rats results in different times of PPL permanence in plasma 2. In addition, piperlongumine has no Lipinski’s and Lead-like rule violations 5, which makes this molecule an excellent candidate to be launched as a drug. This molecule is characterized by the presence of electrophilic frames 3 and α,β-unsaturated amide as Michael acceptor 4. Piperlongumine (PPL) is a lipophilic molecule, with logP = 1.63 calculated through the software Marvin (ChemAxon, Budapest, Hungary). This natural compound has been calling attention of scientific community because of its biological activities such as antitumor, antimetastatic, antiplatelet aggregation and anxiolytic 2. Piperlongumine, also known as piplartine, is an amide alkaloid isolated from Long pepper 1 that is widely used in Indian traditional medicine. The stability of the RSA-PPL complex was checked by molecular dynamics. The molecular docking described the microenvironment of the interaction sites, rich in apolar residues. Interaction density function method (IDF) indicated that PPL accessed two cooperative sites in RSA, with moderate binding constants (2.3 × 10 5 M −1 and 1.3 × 10 5 M −1). Thermodynamic parameters revealed that PPL binds to RSA spontaneously (ΔG < 0) and the process is entropically driven. This paper shows the importance of applying inner filter correction over the entire fluorescence spectrum prior to any conclusion regarding changes in the polarity of the fluorophore microenvironment, also demonstrates the convergence of the results obtained from the treatment of fluorescence data using the area below the spectrum curve and the intensity in a single wavelength. In this sense, the present study elucidated the mechanism of interaction between PPL and RSA, using in conjunction spectroscopic and computational techniques. Although PPL is present in the bloodstream, no information is found on the interaction between PPL and rat serum albumin (RSA), the most abundant protein with the function of transporting endo/exogenous molecules. In recent pharmacokinetics studies in rats, this molecule reached 76.39% of bioavailability. \) for a short animation.Piperlongumine (PPL) has presented a variety of important pharmacological activities. ![]()
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