title: Molecular interaction study of flavonoid derivative 3d with human serum albumin using multispectroscopic and molecular modeling approach.
abstract: Human serum albumin (HSA) has been developed as a model protein to study drug-protein interaction. In the present work, the interaction between our synthesized flavonoid derivative 3d (possessing potent antitumor activity against HepG2 cells) and HSA was investigated using fluorescence spectroscopy, circular dichroism spectroscopy, UV-vis spectroscopy and molecular modeling approach. Fluorescence spectroscopy showed that the fluorescence of HSA can be quenched remarkably by 3d under physiological condition with a slight shift of maximum fluorescence emission bands from 360nm to 363nm. Calculated results from Stern-Volmer equation and modified Stern-Volmer equation indicated that the fluorescence was quenched by static quenching processing with association constant 5.26±0.04×10(4)L mol(-1) at 298K. After comprehensive consideration of the free energy change ΔG, enthalpy change ΔH and entropy change ΔS, electrostatic interactions were confirmed as the main factor that participate in stabilizing the 3d-HSA complex. Both dichroism spectroscopy and UV-vis spectroscopy indicated conformational change of HSA after binding to 3d. Moreover, the structure of HSA was loosened and the percentage of α-helix decreased with increasing concentration of 3d. Molecular modeling results demonstrated that 3d could bind to HSA well into subdomain IIA, which is related to its capability of deposition and delivery. Three cation-π interactions and three hydrogen bonds occurred between 3d and amino acid residuals ARG218, ARG222 and LYS199. In conclusion, flavonoid derivative 3d can bind to HSA with noncovalent bond in a relatively stable way, so it can be delivered by HSA in a circulatory system.
authors.affiliation: Department of Chemistry, Tsinghua University, Beijing 100084, China; State Key Laboratory Breeding Base-Shenzhen Key Laboratory of Chemical Biology, Graduate School at Shenzhen, Tsinghua University, Shenzhen 518055, China; Key Laboratory of Metabolomics at Shenzhen, Shenzhen 518055, China.
authors.forename: Juntong
authors.initials: J
authors.lastname: Wei
authors.affiliation: State Key Laboratory Breeding Base-Shenzhen Key Laboratory of Chemical Biology, Graduate School at Shenzhen, Tsinghua University, Shenzhen 518055, China; Neptunus Pharmaceutical Technology Center, Shenzhen 518057, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Jin
authors.affiliation: Department of Chemistry, Tsinghua University, Beijing 100084, China; State Key Laboratory Breeding Base-Shenzhen Key Laboratory of Chemical Biology, Graduate School at Shenzhen, Tsinghua University, Shenzhen 518055, China; Key Laboratory of Metabolomics at Shenzhen, Shenzhen 518055, China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Wu
authors.affiliation: State Key Laboratory Breeding Base-Shenzhen Key Laboratory of Chemical Biology, Graduate School at Shenzhen, Tsinghua University, Shenzhen 518055, China; School of Medicine, Tsinghua University, Beijing 100084, China.
authors.forename: Yuyang
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: State Key Laboratory Breeding Base-Shenzhen Key Laboratory of Chemical Biology, Graduate School at Shenzhen, Tsinghua University, Shenzhen 518055, China; Key Laboratory of Metabolomics at Shenzhen, Shenzhen 518055, China. Electronic address: gao.dan@sz.tsinghua.edu.cn.
authors.forename: Dan
authors.initials: D
authors.lastname: Gao
authors.affiliation: State Key Laboratory Breeding Base-Shenzhen Key Laboratory of Chemical Biology, Graduate School at Shenzhen, Tsinghua University, Shenzhen 518055, China; Key Laboratory of Metabolomics at Shenzhen, Shenzhen 518055, China. Electronic address: liuhx@sz.tsinghua.edu.cn.
authors.forename: Hongxia
authors.initials: H
authors.lastname: Liu
mesh_terms: D000465:Algorithms; D001120:Arginine / Q000737:chemistry / Q000378:metabolism; D002942:Circular Dichroism; D005419:Flavonoids / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D006860:Hydrogen Bonding; D007700:Kinetics; D008239:Lysine / Q000737:chemistry / Q000378:metabolism; D008958:Models, Molecular; D015394:Molecular Structure; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D012709:Serum Albumin / Q000737:chemistry* / Q000378:metabolism; D013050:Spectrometry, Fluorescence; D013053:Spectrophotometry; D013057:Spectrum Analysis / Q000379:methods*
chemical_list: D005419:Flavonoids; D012709:Serum Albumin; D001120:Arginine; D008239:Lysine
keywords: Flavonoid derivative; Human serum albumin (HSA); Molecular docking; Spectrum