title: Molecular mechanism of the binding of 3,4,5-tri-O-caffeoylquinic acid to human serum albumin: Saturation transfer difference NMR, multi-spectroscopy, and docking studies.
abstract: As a natural dietary polyphenol, 3,4,5-tri-O-caffeoylquinic acid (3,4,5-triCQA) exhibits numerous stronger pharmacological activities than that of its analogues. Studies on interaction between 3,4,5-triCQA and protein are very helpful for understanding the mechanism of these enhanced biological functions. In this study,1H saturation transfer difference NMR (1H STD-NMR) combined with multi-spectroscopy were used to probe the interaction of 3,4,5-triCQA with human serum albumin (HSA). Both qualitative and quantitative1H STD-NMR indicated that 3,4,5-triCQA can specifically bind to HSA at the favored Sudlow's site II with caffeoyl groups as the main recognizable moiety. Fluorescence emission spectra showed that Stern-Volmer quenching constant (KSV) decreases from 10.132×104M-1to 9.711×104M-1with temperature raise, indicating that 3,4,5-triCQA quenches HSA fluorescence through a static mechanism. Binding constant (Kb=5.557×105M-1) and the number of binding sites (n≈1) at 298K suggested that 3,4,5-triCQA only occupies one site in HSA with high affinity. Enthalpy (ΔH=-28.802kJ/mol) and entropy (ΔS=12.429J/mol/K) change proved the dominant role of electrostatic interaction in binding process. Multi-spectroscopic analysis also confirmed that the protein secondary structure and hydrophobicity were significantly affected. Molecular docking further verified the NMR and spectroscopic results. Overall, 3,4,5-triCQA exhibited a strong albumin affinity owing to the plural caffeoyl groups, which lead to the enhanced pharmacological activities. This study clarified the molecular mechanism of 3,4,5-triCQA in binding to HSA, and the findings are beneficial for the research on polyphenol-like drugs and antioxidants in foods or cosmetics.
authors: College of Chemical Engineering, Sichuan University, Chengdu 610065, PR China.
authors: Bin
authors: B
authors: Tang
authors: College of Chemical Engineering, Sichuan University, Chengdu 610065, PR China.
authors: Yanmei
authors: Y
authors: Huang
authors: College of Chemical Engineering, Sichuan University, Chengdu 610065, PR China.
authors: Hongqin
authors: H
authors: Yang
authors: College of Chemical Engineering, Sichuan University, Chengdu 610065, PR China.
authors: Peixiao
authors: P
authors: Tang
authors: College of Chemical Engineering, Sichuan University, Chengdu 610065, PR China. Electronic address: lihuilab@sina.com.
authors: Hui
authors: H
authors: Li
mesh_terms: D006801:Humans; D062105:Molecular Docking Simulation; D011801:Quinic Acid / Q000031:analogs & derivatives* / Q000737:chemistry; D012709:Serum Albumin / Q000737:chemistry*; D013057:Spectrum Analysis / Q000379:methods*; D013816:Thermodynamics
chemical_list: D012709:Serum Albumin; C472707:caffeoylquinic acid; D011801:Quinic Acid
keywords: Human serum albumin; Molecular docking; NMR; Polyphenol; Saturation transfer difference; Spectroscopy