Novel binding studies of human serum albumin with trans-feruloyl maslinic acid

Department of Biochemistry, School of Life Sciences, University of Hyderabad, Hyderabad 500046, India.
Journal of photochemistry and photobiology. B, Biology (Impact Factor: 2.96). 02/2009; 95(2):81-8. DOI: 10.1016/j.jphotobiol.2009.01.002
Source: PubMed


Human serum albumin (HSA) is a predominant protein in the blood. Most drugs can bind to HSA and be transported to target locations of the body. For this study, we have extracted 3-trans-feruloyl maslinic acid (FMA) from the medicinal plant Tetracera asiatica, its a non-fluorescent derivative have potent anti-cancer, anti-HIV, anti-diabetic, and anti-inflammatory activities. The binding constant of the compound with HSA, calculated from fluorescence data, was found as K(FMA)=1.42+/-0.01 x 10(8) M(-1), which corresponds to 10.9 kcal M(-1) of free energy. Furthermore, microTOF-Q mass spectrometry data showed binding of FMA at nanomolar concentrations of FMA to free HSA. The study detected a mass increase from 66,560 Da (free HSA) to 67,919 Da (HSA+drug). This indicated a strong binding of FMA to HSA, resulting in an increase of the protein's absorbance and fluorescence. The secondary structure of HSA+FMA (0.1 mM) complexes showed the protein secondary structure became partially unfolded upon interaction of FMA with HSA, as well as indicating that HSA-FMA complexes were formed. Docking experiments uncovered the binding mode of FMA in HSA molecule. It was found that FMA binds strongly in different places with hydrogen bonding at IB domain of Arg 114, Leu 115 and Asp 173.

Download full-text


Available from: Babu Sudhamalla,
  • Source
    • "Among serum albumins, bovine serum albumin (BSA) has the advantages of low cost, stability, ready availability, and unusual ligand-binding properties. Despite the ample literature, however, little firm knowledge is available on the binding between albumin and triterpenoids [14] [15] [16] [17], especially on structure-affinity relationship of these compounds with albumin. Clearly, an understanding of the interaction of these pharmaceuticals with albumin is needed to gain insight into their therapeutic effectiveness. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Steady-state and time-resolved fluorescence, as well as Fourier transform-infrared (FT-IR) spectroscopy studies were made to understand the interaction between diacetyl maslinic acid (DMA) and bovine serum albumin (BSA) at pH 7.4. A decrease in fluorescence intensity and a blue shift of the emission peak were observed in the DMA–BSA complex, which were attributed to changes in the microenvironment of the protein fluorophores. Spectroscopic analysis revealed that the fluorescence-quenching mechanism between DMA and BSA was a static procedure. Displacement experiments with site markers indicated that DMA binds to BSA at Sudlow's site I (subdomain IIA). Binding constants for the protein–drug interaction were determined at three different temperatures (298, 305, and 310 K). Enthalpy (ΔH 0) and entropy (ΔS 0) changes indicated that hydrophobic interactions were the dominant intermolecular forces in the binding of DMA to BSA. The interaction appears to be entropy-driven, and the process spontaneous and endothermic. Enthalpy–entropy compensation suggests that reorganization of water molecules plays an important role. Anisotropy and FT-IR experiments revealed that BSA loses its structure in the presence of DMA. The secondary structure compositions of free BSA and DMA–BSA complex were determined by FT-IR. The binding distance and transfer efficiency for DMA–BSA complex were calculated according to the Föster theory of non-radiative energy transfer.
    Journal of Molecular Liquids 04/2015; 208. DOI:10.1016/j.molliq.2015.04.050 · 2.52 Impact Factor
  • Source
    • "Tajmir - Riahi , 2009 ; Pu , Jiang , & Chen , 2013 ; Sułkow - ska , 2002 ) . Recently , we have reported quenching of HSA fluorescence with biologically significant drug candidates ( Garg et al . , 2013 ; Gokara et al . , 2010 ; Gokara et al . , 2013 ; Subramanyam et al . , 2009b ; Sudhamalla et al . , 2010 ) . With an increasing concentration of chitooligomers with HSA and AGP , the absorption at excitation ( 285 nm ) and emission ( 360 nm ) wavelength introduces inner filter effect that may decrease the fluorescence intensity and results in a nonlinear relationship between the observed fluorescence intensity a"
    [Show abstract] [Hide abstract]
    ABSTRACT: Chitosan is a naturally occurring deacetylated derivative of chitin with versatile biological activities. Here, we studied the interaction of chitosan oligomers with low degree of polymerization such as chitosan monomer (CM), chitosan dimer (CD), and chitosan trimer (CT) with human serum albumin (HSA) a major blood carrier protein and α-1-glycoprotein (AGP). Since, HSA and AGP are the two important plasma proteins that determine the drug disposition and affect the fate of distribution of drugs. Fluorescence emission spectra indicated that CM, CD, and CT had binding constants of KCM = 6.2 ± .01 × 10(5) M(-1), KCD = 5.0 ± .01 × 10(4) M(-1), and KCT = 1.6 ± .01 × 10(6) M(-1), respectively, suggesting strong binding with HSA. However, binding of chitooligomers with AGP was insignificant. Thermodynamic and molecular docking analysis indicated that hydrogen bonds and also hydrophobic interaction played an important role in stabilizing the HSA-chitooligomer complexes with free energies of -7.87, -6.35, and -8.4 Kcal/mol for CM, CD, and CT, respectively. Further, circular dichroism studies indicated a minor unfolding of HSA secondary structure, upon interaction with chitooligomers, which are supported with fluctuations of root mean square deviation (RMSD) and radius of gyration (Rg) of HSA. Docking analysis revealed that all three chitooligomers were bound to HSA within subdomain IIA (Site I). In addition, RMSD and Rg analysis depicted that HSA-chitooligomer complexes stabilized at around 4.5 ns. These results suggest that HSA might serve as a carrier in delivering chitooligomers to target tissues than AGP which has pharmacological importance.
    Journal of biomolecular Structure & Dynamics 12/2013; 33(1). DOI:10.1080/07391102.2013.868321 · 2.92 Impact Factor
  • Source
    • "Fluorescence quenching of the protein upon drug binding was used to find the drug-protein interactions and measure the binding affinity of the drug to HSA [53]. Figure 2 depicts the room temperature fluorescence emission spectra of HSA obtained fluorescence maximum at 362 nm, which is in agreement with our previous reports [30], [31]. In the presence of different concentrations of coumarin derivatives (0.001 to 0.01 mM) with the physiological phosphate buffer pH 7.2, our results showed that, with the increasing concentrations of coumarin derivatives and a fixed concentration of HSA (0.001 mM), the maximum fluorescence (362 nm) of HSA was quenched upon binding of coumarin derivatives (Figure 2). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Coumarin is a benzopyrone which is widely used as an anti-coagulant, anti-oxidant, anti-cancer and also to cure arthritis, herpes, asthma and inflammation. Here, we studied the binding of synthesized coumarin derivatives with human serum albumin (HSA) at physiological pH 7.2 by using fluorescence spectroscopy, circular dichroism spectroscopy, molecular docking and molecular dynamics simulation studies. By addition of coumarin derivatives to HSA the maximum fluorescence intensity was reduced due to quenching of intrinsic fluorescence upon binding of coumarin derivatives to HSA. The binding constant and free energy were found to be 1.957±0.01×10(5) M(-1), -7.175 Kcal M(-1) for coumarin derivative (CD) enamide; 0.837±0.01×10(5) M(-1), -6.685 Kcal M(-1) for coumarin derivative (CD) enoate, and 0.606±0.01×10(5) M(-1), -6.49 Kcal M(-1) for coumarin derivative methylprop (CDM) enamide. The CD spectroscopy showed that the protein secondary structure was partially unfolded upon binding of coumarin derivatives. Further, the molecular docking studies showed that coumarin derivatives were binding to HSA at sub-domain IB with the hydrophobic interactions and also with hydrogen bond interactions. Additionally, the molecular dynamics simulations studies contributed in understanding the stability of protein-drug complex system in the aqueous solution and the conformational changes in HSA upon binding of coumarin derivatives. This study will provide insights into designing of the new inspired coumarin derivatives as therapeutic agents against many life threatening diseases.
    PLoS ONE 05/2013; 8(5):e63805. DOI:10.1371/journal.pone.0063805 · 3.23 Impact Factor
Show more