Interaction Of Human Serum Albumin Research Articles

Probing the Interaction of Human Serum Albumin with Ciprofloxacin in the Presence of Silver Nanoparticles of Three Sizes: Multispectroscopic and ζ Potential Investigation

The binding of ciprofloxacin to human serum albumin (HSA) in the presence and absence of silver nanoparticles of three sizes was investigated for the first time. For this purpose fluorescence spectroscopy, circular dichroism, UV-vis spectroscopy, and ζ potential techniques were employed under physiological conditions. The titration results indicated that ciprofloxacin quenched the fluorescence intensity of HSA through a static mechanism, but in the presence of Ag nanoparticles of sizes I and II there were two different kinds of interaction behavior. Results of circular dichroism indicated that the secondary structure of HSA was modified with increasing ciprofloxacin concentration. A comparison between resonance light scattering of binary and ternary systems allowed us to estimate the effect of silver nanoparticles on the initial formation and aggregation of ciprofloxacin with HSA. The ζ-potential results suggested induced conformational changes on HSA, thus confirming the experimental and theoretical results.

Binding of Phthalate Plasticizers to Human Serum Albumin in Vitro: A Multispectroscopic Approach and Molecular Modeling

As endocrine-disrupting chemicals, a few frequently used phthalate plasticizers were banned or restricted for use as additives in food in some countries. The interaction mechanisms between three phthalate plasticizers with human serum albumin (HSA) were studied by fluorescence (quenching, synchronous, and three-dimensional), UV-vis absorption, circular dichroism (CD), and Fourier transform infrared (FT-IR) spectroscopy, in combination with molecular modeling under simulative physiological conditions, respectively. The results obtained from fluorescence quenching data revealed that the plasticizers-HSA interaction altered the conformational strcture of HSA. Meanwhile, the alterations of HSA secondary structure in the presence of phthalate plasticizers were investigated. The binding distances for the plasticizers-HSA system were provided by the efficiency of fluorescence resonance energy transfer. Furthermore, the thermodynamic analysis implied that hydrophobic forces were the main interaction for the plasticizers-HSA system, which agreed well with the results from the molecular modeling study.

Selective Binding of Albumin to Gm1 Ganglioside Micelles Containing Paclitaxel

In our previous work we showed that taxanes (paclitaxel (Ptx) and docetaxel(Dtx)) can be spontaneously loaded into monosialoganglioside (GM1) nanomicelles, increasing their water solubility about 6,000 times, to render stable water soluble formulations that could be used as a novel strategy to deliver drugs in cancer. Here, we describe the hydrophobic interaction of Human Serum Albumin (HSA) with GM1 micelles loaded with Ptx, as a strategy that could improve tumour drug accumulation. This interaction is regulated by conditions such pH and temperature and generates ternary complexes GM1/Ptx/HSA with sizes around 19 to 24 nm and hydrodynamic radius equivalent to a globular protein of 140-180 kDa. These mixed micelles were stable in solution for at least 40 days and also upon freeze-thawing or lyophilization-solubilization cycles. The results of in vitro assays showed that the nano-structures developed are taken up by cell cultures with an antimitotic activity of Ptx on tumoral and nontumoral cell lines that was similar to that observed with the free drug in DMSO solution.

Fluoxetine competes with cortisol for binding to human serum albumin.

Human serum albumin (HSA) is an important protein that carries variety of substances like some hormones and drugs in blood. Pharmacological studies of the interaction of many drugs and HSA are reported during several decades, specially recently years. Interaction of cortisol and fluoxetine hydrochloride (FLX) (as a common anti-stress drug) with HSA (as their carrier in blood) has been studied separately by using different spectroscopic techniques. Here, considering the increment of anti-stress drugs consumption, conformational change of HSA in presence of cortisol and FLX in 50 mM tris buffer, at pH = 7.5 and 37°C, is investigated via pH meter, UV absorption and fluorescence spectroscopy and circular dichroism methods. pH meter findings indicate that the acid denaturation of HSA in the presence of drug and cortisol occurs in the similar manner and this pattern is different relative to the denaturation of HSA in the absence of two reagents. The results of the other techniques consistent with the pH meter findings show that FLX effects on the physiochemical properties of HSA are as that of Cortisol. In-vivo study in Rats confirms in-vitro findings which means blood cortisol level increased in the presence of FLX. Experimental results indicate that FLX and cortisol alter the structural aspects of HSA in similar manner, so, this findings lead to the following reasonable conclusion: "FLX is a competitive ligand for the binding of cortisol to HSA. Binding of FLX to HSA interferes to the interaction of cortisol-HSA."

Study on the interaction between tabersonine and human serum albumin by optical spectroscopy and molecular modeling methods

The mechanism of interaction between tabersonine (TAB) and human serum albumin (HSA) was investigated by the methods of fluorescence spectroscopy, UV–vis absorption spectroscopy and molecular modeling under simulative physiological conditions. Results obtained from analysis of fluorescence spectrum and fluorescence intensity indicated that TAB has a strong ability to quench the intrinsic fluorescence of HSA through a static quenching procedure. The binding site number n and apparent binding constant K a , corresponding thermodynamic parameters Δ G, Δ H and Δ S at different temperatures were calculated. The distance r between donor (human serum albumin) and acceptor (tabersonine) was obtained according to the Förster theory of non-radiation energy transfer. The effect of common ions on binding constant was also investigated. The synchronous fluorescence and three-dimensional fluorescence spectra were used to investigate the structural change of HSA molecules with addition of TAB. Furthermore, the study of molecular modeling indicated that TAB could bind to the site I of HSA and hydrophobic interaction was the major acting force, which was in agreement with the binding mode study.

Interaction between phillygenin and human serum albumin based on spectroscopic and molecular docking

In this paper, the interaction of human serum albumin (HSA) with phillygenin was investigated by fluorescence, circular dichroism (CD), UV–vis spectroscopic and molecular docking methods under physiological conditions. The Stern–Volmer analysis indicated that the fluorescence quenching of HSA by phillygenin resulted from static mechanism, and the binding constants were 1.71 × 10 5, 1.61 × 10 5 and 1.47 × 10 4 at 300, 305 and 310 K, respectively. The results of UV–vis spectra show that the secondary structure of the protein has been changed in the presence of phillygenin. The CD spectra showed that HSA conformation was altered by phillygenin with a major reduction of α-helix and an increase in β-sheet and random coil structures, indicating a partial protein unfolding. The distance between donor (HSA) and acceptor (phillygenin) was calculated to be 3.52 nm and the results of synchronous fluorescence spectra showed that binding of phillygenin to HSA can induce conformational changes in HSA. Molecular docking experiments found that phillygenin binds with HSA at IIIA domain of hydrophobic pocket with hydrogen bond interactions. The ionic bonds were formed with the O (4), O (5) and O (6) of phillygenin with nitrogen of ASN109, ARG186 and LEU115, respectively. The hydrogen bonds are formed between O (2) of phillygenin and SER419. In the presence of copper (II), iron (III) and alcohol, the apparent association constant K A and the number of binding sites of phillygenin on HSA were both decreased in the range of 88.84–91.97% and 16.09–18.85%, respectively. In view of the evidence presented, it is expected to enrich our knowledge of the interaction dynamics of phillygenin to the important plasma protein HSA, and it is also expected to provide important information of designs of new inspired drugs.

A novel approach of interaction between bilirubin and human serum albumin in the presence of Aspirine

Introduction: Bilirubin (BR), the yellow neurotoxic pigment of jaundice and the end product of heme metabolism in mammals, is lipophilic tetrapyrrole dicarboxylic acid. Human serum albumin (HSA) is a principal extra cellular protein. Its primary pharmacokinetics function is participating in absorption, distribution, metabolism and excretion of drug. Acetylsalicylic acid (ASA) has been shown to reduce the risk for colorectal cancer by as much as approximately 40%, a property that is shared by other nonsteroidal anti-inflammatory drugs. Materials and methods: BR, ASA and HSA were purchased from Sigma. Fluorescence measurements were carried out on a F-2500. Molecular modeling was done by autodock software. Result and discussion: Investigating the interaction of drugs to HSA can elucidate the properties of drug–protein complex. Synchronous fluorescence spectroscopy from the interaction of HSA with BR and in the presence of Aspirin showed that ligand affect the conformation of HSA. Interaction of BR and ASA with HSA changed the binding affinity of second drug that can use the location in the binding site on protein. On the other hand we found that the binding affinity of ASA bound to HAS was stronger in the presence of BR, and considered the same result for addition of ASA to HAS-BR complex.

Study on the interaction of tamiflu and oseltamivir carboxylate with human serum albumin

Oseltamivir phosphate (OP; tamiflu) is an antiviral pro-drug, which is hydrolyzed hepatically to the active metabolite oseltamivir carboxylate (OC). It is the first orally neuraminidase inhibitor that was used in the treatment and prophylaxis of influenza virus A and B infection. Human serum albumin (HSA) is the most abundant of the proteins in the blood plasma and is major transporter for delivering several drugs in vivo. This study was designed to examine the interaction of HSA with oseltamivir phosphate (OP) and oseltamivir carboxylate (OC) in aqueous solution at physiological conditions, using a constant protein concentration and various drug contents. FTIR, UV–Vis spectroscopic methods were used to determine the drugs binding mode, the binding constant and the effects of drug complexation on protein secondary structure. Structural analysis showed that OP and OC bind HSA via polypeptide polar groups with overall binding constants of K OP–HSA = 3.86(±1.05) × 10 3 M −1 and K OC–HSA = 1.5(±0.45) × 10 2 M −1. The alterations of protein secondary structure are attributed to a partial destabilization of HSA on drug complexation. The protein secondary structure showed no major alterations at low drugs concentrations (50 μM), whereas at higher content (1 mM), decrease of α-helix from 58% (free HSA) to 38% (OP–HSA)–48% (OC–HSA), decrease of random coil from 15% (free HSA) to 2% (OP–HSA)–3% (OC–HSA), increase of β-sheet from 6% (free HSA) to 20% (OC–HSA)–29% (OP–HSA) and turn from 8% (free HSA) to 17% (OC–HSA)–19% (OP–HSA) occurred in the drug–HSA complexes. These observations indicated that low drug content induced protein stabilization, whereas at high drug concentration, a partial protein destabilization occurred in these drug–HSA complexes.

Spectroscopic Investigated to the Interaction of Human Serum Albumin with Fluorescence Carbon Nanoparticles

The interaction of SiO2 including carbon nanoparticles (CNPs) with human serum albumin (HSA) in vitro under simulated physiological conditions has been studied by fluorescence methods and dynamic light scattering (DLS). Experimental results indicated that SiO2 including CNPs can be stabilized in the physiological environment and emit fluorescence, which quench HSA fluorescence by a static quenching mechanism. Our findings indicate that understanding the interaction between proteins and carbon nanoparticles is crucial for toxicological studies.

Study on the interaction of phthalate esters to human serum albumin by steady-state and time-resolved fluorescence and circular dichroism spectroscopy

Phthalate esters (PAEs) are globally pervasive contaminants that are considered to be endocrine disruptor chemicals and toxic environmental priority pollutants. In this paper, the interactions between PAEs and human serum albumin (HSA) were examined by molecular modelling, steady state and time-resolved fluorescence, ultraviolet–visible spectroscopy (UV–vis) and circular dichroism spectroscopy (CD). The association constants between PAEs and HSA were determined using the Stern–Volmer and Scatchard equations. The binding of dimethyl phthalate (DMP) to HSA has a single class of binding site and its binding constants ( K) are 4.08 × 10 3, 3.97 × 10 3, 3.45 × 10 3, and 3.20 × 10 3 L mol −1 at 289, 296, 303, and 310 K, respectively. The Stern–Volmer and Scatchard plots both had two regression curves for HSA–butylbenzyl phthalate (BBP) and HSA–di-2-ethylhexyl phthalate (DEHP), which indicated that these bindings were via two types of binding sites: the numbers of binding site for the first type were lower than for the second type. The binding constants of the first type binding site were higher than those of the second type binding site at corresponding temperatures, the results suggesting that the first type of binding site had high affinity and the second binding site involved other sites with lower binding affinity and selectivity. The thermodynamic parameters of the binding reactions (Δ G°, Δ H° and Δ S°) were measured, and they indicated the presences of hydrophobic forces and hydrogen interactions in the PAEs–HSA interactions, which agreed well with the results from molecular modelling. The alterations of protein secondary structure in the presence of PAEs were confirmed by UV–vis and CD spectroscopy. The time-resolved fluorescence study showed that the lifetime of Trp residue of HSA decreased after the addition of PAEs, which implied that the Trp residue of HSA was the main binding site.

Oxidative Damage of Lysozyme and Human Serum Albumin and Their Mixtures. A Comparison of Photosensitized and Peroxyl Radical Promoted Processes

Oxidative modifications of lysozyme (Lyso) and human serum albumin (HSA) mediated by photoinduced processes and peroxyl radicals were studied. Both oxidative conditions were applied to the separate proteins and their mixtures. Dimerization and fragmentation of the proteins do not correlate with the formation of carbonyls or peroxides, implying that evaluation of these changes is not an index of the overall oxidative modification of a protein. The results obtained also show that the hypothesis that the electrostatic interactions of Lyso and HSA could facilitate the formation of Lyso-HSA dimers in the presence of a source of reactive oxygen species was verified in both ROS-producing systems.

Aggregation of Human Serum Albumin on Graphite and Single-Walled Carbon Nanotubes as Studied by Scanning Probe Microscopies

Human serum albumin (HSA) is the most abundant protein in blood plasma showing a remarkable ability to bind a broad range of hydrophobic substrates. We employed scanning tunneling microscopy and atomic force microscopy to characterize the morphology of HSA aggregates on highly-ordered pyrolytic graphite (HOPG) and single-walled carbon nanotubes (SWNTs). The morphologies found for albumin aggregates on HOPG are quite different from the ones observed on SWNTs. On HOPG, HSA forms aggregates of roughly 10-20 molecules; single protein molecules were observed as well. In the case of SWNTs, nanotubes were partially or totally covered with HSA, exhibiting four general types of aggregation: (i) SWNT sidewalls contain single molecules of albumin which are away from each other at distances longer than the HSA molecular size; (ii) SWNTs are completely covered with HSA, which forms a thin and relatively homogeneous layer; (iii) SWNTs have a complete layer of HSA with additional accumulation of protein at separate sites; and (iv) several SWNTs totally covered with albumin assemble into a bundle-like structure common for bare nanotubes. These observations are interpreted in terms of stronger interactions of HSA with nanotube sidewalls than with flat graphite surface.

Separate and simultaneous binding effects of aspirin and amlodipine to human serum albumin based on fluorescence spectroscopic and molecular modeling characterizations: A mechanistic insight for determining usage drugs doses

The binding of aspirin (ASA) and amlodipine (AML) to human serum albumin (HSA) in aqueous solution was investigated by multiple techniques such as fluorescence quenching, resonance light scattering (RLS), three-dimensional fluorescence spectroscopy, FT-IR and zeta-potential measurements in an aqueous solution at pH=7.4. For the protein–ligand association reaction, fluorescence measurements can give important clues as to the binding of ligands to proteins, e.g., the binding mechanism, binding mode, binding constants, binding sites, etc. Fluorescence spectroscopy showed that ASA and AML could quench the HSA fluorescence spectra, and this quenching effect became more significant when both ASA and AML coexisted. The results pointed at the interaction between HSA and both drugs as ternary systems decreasing the binding constant and binding stability of the HSA–drug complex as a binary system. Therefore, by reducing the amount of drugs transported to their targets, the free drug concentration of the target would be reduced, lowering the efficacy of the drugs. It was demonstrated that there exists antagonistic behavior between the two drugs when it comes to binding of HSA. Furthermore, the fluorescence results also showed that the quenching mechanism of HSA–drug complexes as binary and ternary systems is a static procedure. The number of binding sites of HSA–ASA, (HSA–AML)ASA, HSA–AML and (HSA–ASA) AML were 1.31, 0.92, 1 and 0.93, respectively. Due to the existence of the antagonistic action between ASA and AML, the binding distance r was reduced. The results of synchronous fluorescence and three-dimensional fluorescence spectra showed that the antagonistic action between ASA and AML would alter the micro-environment around Trp and Tyr residues. Moreover, the simultaneous presence of ASA and AML during binding to HSA should be taken into account in multidrug therapy, as it induces the necessity of a monitoring therapy owing to the possible increase of uncontrolled toxic effects. Molecular dynamic studies showed that the affinity of each of the drugs to HSA was reduced in the presence of significant amounts of the other. In the interaction of HSA with both drugs, the zeta potential of the ternary system is more negative than its binary counterpart. The zeta-potential results suggested induced conformational changes on HSA that confirmed the experimental and theoretical results.

Binding of antitumor tamoxifen and its metabolites 4-hydroxytamoxifen and endoxifen to human serum albumin

Tamoxifen is extensively metabolized, and several metabolites have been detected in human serum. The aim of this study was to examine the interaction of human serum albumin (HSA) with tamoxifen and its metabolites 4-hydroxytamoxifen and endoxifen at physiological conditions, using constant protein concentration and various drug contents. FTIR, UV–Visible, CD and fluorescence spectroscopic methods as well as molecular modeling were used to analyse drug binding mode, the binding constant and the effects of drug complexation on HSA stability and conformation. Structural analysis showed that tamoxifen and its metabolites bound HSA via both hydrophobic and hydrophilic interactions with overall binding constants of K tam = 1.8 (±0.2) × 10 4 M −1, K 4-hydroxytam = 1.8 (±0.4) × 10 4 M −1 and K endox = 2.0 (±0.5) × 10 4 M −1. The number of bound drugs per protein is 1.2 (tamoxifen), 1.7 (4-hydroxitamoxifen) and 1.0 (endoxifen). Structural modeling showed the participation of several amino acid residues in drug–HSA complexation, with extended H-bonding network. HSA conformation was altered by tamoxifen and its metabolites with a major reduction of α-helix and an increase in β-sheet, random coil and turn structures, indicating a partial protein unfolding. Our results suggest that serum albumins can act as carrier proteins for tamoxifen and its metabolites in delivering them to target tissues.

Investigation of the mechanism of binding of thiacloprid to human serum albumin using spectroscopic techniques and molecular modeling methods

Fluorescence spectroscopy, UV absorption, circular dichroism (CD) spectroscopy and molecular modeling methods were used to characterize the binding properties of thiacloprid (TL) with human serum albumin (HSA) at molecular level under physiological conditions. The fluorescence intensity of HSA decreased regularly with the gradually increasing concentration of thiacloprid. The binding constant K at three different temperatures (290, 300 and 310 K) were 3.07, 2.74 and 1.35 × 104 M−1, respectively, for TL–HSA interaction have been calculated from the relevant fluorescence data. CD spectroscopic measurements have shown that the secondary structures of the protein have been changed by the interaction of thiacloprid with HSA. Furthermore, the study of molecular modeling indicated that thiacloprid could be located on the surface of the binding pocket of subdomains IIA in HSA. The hydrophobic interaction was the major acting force and there are H-bonds and electrostatic interactions between TL and HSA, which is in good agreement with the results from the experimental thermodynamic parameters (the enthalpy change ΔH0 and the entropy change ΔS0 were calculated to be -20.378 kJ/mol and 16.328 J/mol K according to the Van9t Hoff equation).

Investigation of the mechanism of binding of thiacloprid to human serum albumin using spectroscopic techniques and molecular modeling methods

Fluorescence spectroscopy, UV absorption, circular dichroism (CD) spectroscopy and molecular modeling methods were used to characterize the binding properties of thiacloprid (TL) with human serum albumin (HSA) at molecular level under physiological conditions. The fluorescence intensity of HSA decreased regularly with the gradually increasing concentration of thiacloprid. The binding constant K at three different temperatures (290, 300 and 310 K) were 3.07, 2.74 and 1.35 × 104M−1, respectively, for TL–HSA interaction have been calculated from the relevant fluorescence data. CD spectroscopic measurements have shown that the secondary structures of the protein have been changed by the interaction of thiacloprid with HSA. Furthermore, the study of molecular modeling indicated that thiacloprid could be located on the surface of the binding pocket of subdomains IIA in HSA. The hydrophobic interaction was the major acting force and there are H-bonds and electrostatic interactions between TL and HSA, which is in good agreement with the results from the experimental thermodynamic parameters (the enthalpy change ΔH0and the entropy change ΔS0were calculated to be -20.378 kJ/mol and 16.328 J/mol K according to the Van9t Hoff equation).

Phenotypic Characterization of the Binding of Tetracycline to Human Serum Albumin

Because of the widely usage of the veterinary drug tetracycline (TC), its residue exist extensively in the environment (e.g., animal food, soils, surface water, and groundwater) and can enter human body, being potential harmful. Human serum albumin (HSA) is a major transporter for endogenous and exogenous compounds in vivo. The aim of this study was to examine the interaction of HSA with TC through spectroscopic and molecular modeling methods. The inner filter effect was eliminated to get accurate binding parameters. The site marker competition experiments revealed that TC binds to site II (subdomain IIIA) of HSA mainly through electrostatic interaction, illustrated by the calculated negative ΔH° and ΔS°. Furthermore, molecular docking was applied to define the specific binding sites, the results of which show that TC mainly interacts with the positively charged amino acid residues Arg 410 and Lys 414 predominately through electrostatic force, in accordance with the conclusion of thermodynamic analysis. The binding of TC can cause conformational and some microenvironmental changes of HSA, revealed by UV-visible absorption, synchronous fluorescence, and circular dichroism (CD) results. The accurate and full basic data in the work is beneficial to clarifying the binding mechanism of TC with HSA in vivo and understanding its effect on protein function during the blood transportation process.

Study on the interaction of catechins with human serum albumin using spectroscopic and electrophoretic techniques

The interaction between eight naturally occurring flavanols (catechin, epicatechin, gallocatechin, epigallocatechin, catechin gallate, epicatechin gallate, gallocatechin gallate, and epigallocatechin gallate) and human serum albumin (HSA) has been investigated by spectroscopic (fluorescence quenching and UV–Vis absorption) and electrophoretic (native and SDS PAGE) techniques under simulated physiological conditions (pH 7.40, 37 °C). The spectroscopic results confirmed the complex formation for the tested systems. The binding constants and the number of binding sites were obtained by analysis of fluorescence data. The strongest binding affinity to HSA was found for epicatechin gallate and decreased in the order epicatechin gallate ⩾ catechin gallate > epigallocatechin gallate > gallocatechin gallate ≫ epicatechin ⩾ catechin > gallocatechin ⩾ epigallocatechin. All free energy changes possessed negative sign indicating the spontaneity of catechin–HSA systems formation. The binding distances between the donor (HSA) and the acceptors (catechins) estimated by the Förster theory revealed that non-radiation energy transfer from HSA to catechins occurred with high possibility. According to results obtained by native PAGE, the galloylated catechins increased the electrophoretic mobility of HSA, which indicated the change in the molecular charge of HSA, whilst the non-galloylated catechins caused no changes. The ability of aggregation and cross-linking of tested catechins with HSA was not proved by SDS–PAGE. The relationship between the structure characteristics of all tested catechins (e.g. presence of the galloyl moiety on the C-ring, the number of hydroxyl groups on the B-ring, and the spatial arrangement of the substituents on the C-ring) and their binding properties to HSA is discussed. The presented study contributes to the current knowledge in the area of protein–ligand binding, particularly catechin–HSA interactions.

Interaction and cytotoxicity of mTHPC and mTHPC complexes in Jurkat cells

Objective To investigate the interaction and cytotoxicity of the photosensitizer mTHPC [5, 10, 15, 20-tetrakis (3-hydroxyphenyl) chlorine]and the complex human serum albumin (HSA)-mTHPC in Jurkat cells. Methods Jurkat cells were incubated with different concentrations of mTHPC and HSA-mTHPC for4, 24 and 48 h, followed by illumination with 652 nm for 10 min with 10 mW/cm2. The cellular interaction of free mTHPC and HSA-mTHPC was measured by using flow cytometry. The cytotoxicity was tested using standard toxicity assays (the WST-l-assay for the cell viability, the LDH-assay for the membrane integrity, and the BrdU-assay for the proliferation). Results After incubation with 1.0 mg/L mTHPC for 4 and 24 h, 98.07% and 99.07% of the cells were positive for the photosensitizer. The interaction of HSA without drug with the cells was low. The uptake of mTHPC that was compounded to HSA was as high as of free mTHPC (4 h: 98.13%; 24 h: 99.19%). After illumination, the cell viability was decreased to 13.27%, 5.46% and 4.99% after incubation with 1.0 mg/L mTHPC 4, 24 and 48 h, respectively. The LDH leakage was increased up to 100% even at low concentrations of mTHPC. The cell proliferation was also decreased in a concentration-and time-dependent manner. After incubation with 1.0 mg/L mTHPC for 48 h and subsequent illumination, only marginal proliferation could be detected (0.62% ). Conclusion Both mTHPC and HSA-mTHPC are photosensitizer formulations with potent anti-tumor effects, which can enter tumor cells effectively and cause cell death. HSA nanoparticles can be used as mTHPC carriers. Key words: Photodynamic therapy; Photosensitizer; mTHPC; Jurkat cells

A Theoretical Elucidation of Glucose Interaction with HSA's Domains

The interaction of different domains belonging to Human Serum Albumin (HSA) with open form of glucose have been investigated using molecular dynamics simulation methods. Applying docking, primary structures involving interaction of some residues with glucose have been obtained. Subsequently, equilibrium geometries at 300 K and minimum geometries have been determined for each of aforementioned structures by employing MD simulation and simulated annealing. The stability of species has been evaluated using a SAWSA v2.0 model. Ultimately, NBO analysis has been carried out to specify possible hydrogen bonding regarding the HSA interaction with glucose. Results obtained show that glucose can interact with Lys195, Lys199, and Glu153. In these interactions, each lysine forms an H-bonding with glucose. The H-bonding is obtained by stretching of N-H bond belonging to NH3+ group of lysine along an oxygen atom of glucose. In addition, the above mentioned lysines are protonated, and there is an electrostatic interaction between glucose with Lys195 or Lys199. In addition, an H-bonding is formed between O atom of -COO group belonging to Glu153 and H atom of OH group belonging to glucose. Because, the N-H group of Lys195 interacts with the O atom of latter OH group, reaction of Lys195 is more desirable than that of Lys199. In fact, glucose is placed in the vicinity of Lys195 along with electrostatic interaction and H-bonding to Lys195 and Lys199 as well as H-bonding with Glu153, which subsequently reacts with Lys195. Thus, Lys195 is the primary site in reaction of glucose with HSA.