title: Caffeic acid phenethyl ester exhibiting distinctive binding interaction with human serum albumin implies the pharmacokinetic basis of propolis bioactive components.
abstract: Caffeic acid phenethyl ester (CAPE), as one of the major bioactive components present in propolis, exhibits versatile bioactivities, especially for its potent cytotoxic effects on several cancer cell models. To understand the pharmacokinetic characteristics of CAPE, the binding interaction between CAPE and human serum albumin (HSA) was investigated in vitro using multiple spectroscopic methods and molecular docking. The results reveal that CAPE exhibits a distinctive binding interaction with HSA comparing with other propolis components. The association constant K(A) (L mol(-1)) of the binding reaches 10(6) order of magnitude, which is significantly stronger than the other components of propolis. Based on the theory of fluorescence resonance energy transfer, the binding distance was calculated as 5.7 nm, which is longer than that of the other components of propolis. The thermodynamic results indicate that the binding is mainly driven by hydrogen bonds and van der Waals force. The docking and drugs (warfarin and ibuprofen) competitive results show that CAPE is located in the subdomain IIA (Sudlow's site I, FA7) of HSA, and Gln196 and Lys199 contribute to the hydrogen bonds. Circular dichroism spectra suggest an alteration of the secondary structure of HSA due to its partial unfolding in the presence of CAPE.
authors.affiliation: College of Animal Sciences, Zhejiang University, Hangzhou 310058, China; Zhejiang Provincial Key Laboratory of Biometrology and Inspection & Quarantine, College of Life Sciences, China Jiliang University, Hangzhou 310018, China. Electronic address: atcjlu@126.com.
authors.forename: Hongliang
authors.initials: H
authors.lastname: Li
authors.affiliation: Zhejiang Provincial Key Laboratory of Biometrology and Inspection & Quarantine, College of Life Sciences, China Jiliang University, Hangzhou 310018, China.
authors.forename: Fan
authors.initials: F
authors.lastname: Wu
authors.affiliation: Zhejiang Provincial Key Laboratory of Biometrology and Inspection & Quarantine, College of Life Sciences, China Jiliang University, Hangzhou 310018, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Tan
authors.affiliation: College of Animal Sciences, Zhejiang University, Hangzhou 310058, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Wang
authors.affiliation: College of Animal Sciences, Zhejiang University, Hangzhou 310058, China.
authors.forename: Cuiping
authors.initials: C
authors.lastname: Zhang
authors.affiliation: College of Animal Sciences, Zhejiang University, Hangzhou 310058, China.
authors.forename: Huoqing
authors.initials: H
authors.lastname: Zheng
authors.affiliation: College of Animal Sciences, Zhejiang University, Hangzhou 310058, China. Electronic address: flhu@zju.edu.cn.
authors.forename: Fuliang
authors.initials: F
authors.lastname: Hu
mesh_terms: D002109:Caffeic Acids / Q000737:chemistry*; D002942:Circular Dichroism / Q000379:methods; D031541:Fluorescence Resonance Energy Transfer / Q000379:methods; D006801:Humans; D006860:Hydrogen Bonding; D062105:Molecular Docking Simulation / Q000379:methods; D010626:Phenylethyl Alcohol / Q000031:analogs & derivatives* / Q000737:chemistry; D011429:Propolis / Q000737:chemistry*; D011485:Protein Binding; D017433:Protein Structure, Secondary; D012709:Serum Albumin / Q000737:chemistry*; D013050:Spectrometry, Fluorescence / Q000379:methods; D013816:Thermodynamics
chemical_list: D002109:Caffeic Acids; D012709:Serum Albumin; D011429:Propolis; C055494:caffeic acid phenethyl ester; D010626:Phenylethyl Alcohol
keywords: Binding interaction; Caffeic acid phenethyl ester; Human serum albumin; Molecular docking; Multispectroscopy; Propolis components