Yanmei Huang

Bio: Yanmei Huang is an academic researcher from Sichuan University. The author has contributed to research in topics: Human serum albumin & Docking (molecular). The author has an hindex of 11, co-authored 25 publications receiving 274 citations.

In vitro investigation of the interaction between the hepatitis C virus drug sofosbuvir and human serum albumin through 1H NMR, molecular docking, and spectroscopic analyses

Abstract: Sofosbuvir (SOF), an oral nucleotide inhibitor of the nonstructural protein 5B RNA of the hepatitis C virus (HCV), was approved for treating chronic HCV infection by the Food and Drug Administration in 2013. Understanding drug–protein interactions is a crucial factor in determining the pharmacokinetics and pharmacodynamics of a drug. In this study, the interaction between SOF and human serum albumin (HSA) was investigated using 1H nuclear magnetic resonance (NMR) spectroscopy, the molecular docking method, fluorescence studies, Fourier transform infrared (FT-IR) spectroscopy, and circular dichroism (CD) spectroscopy. The analysis of saturation transfer difference (STD) and WaterLOGSY data indicated that SOF was bound to HSA, and the STD signals showed that the methyl and aromatic protons of the hydrophobic components of SOF have the most intimate contact with protein. The negative free energies (−7.17 kcal mol−1 and −6.18 kcal mol−1) obtained from molecular docking and fluorescence studies clearly suggested the spontaneity of the interaction of the SOF–HSA complex. STD, WaterLOGSY and fluorescence displacement experiments demonstrated that SOF was preferentially bound to site I of HSA, and this finding was supported by the docking results. In addition, synchronous and three-dimensional (3D) fluorescence, FT-IR, and CD spectrocopy provided complementary information on the micro-environmental and conformational changes of HSA with the addition of SOF. The combination of 1H NMR and conventional methods provided useful information to further elucidate the binding mechanisms of antiviral drugs with HSA.

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 quantitative 1H 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-1 to 9.711×104M-1 with 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.

Binding modes of environmental endocrine disruptors to human serum albumin: insights from STD-NMR, ITC, spectroscopic and molecular docking studies.

Abstract: Given that bisphenols have an endocrine-disrupting effect on human bodies, thoroughly exposing their potential effects at the molecular level is important. Saturation transfer difference (STD) NMR-based binding studies were performed to investigate the binding potential of two bisphenol representatives, namely, bisphenol B (BPB) and bisphenol E (BPE), toward human serum albumin (HSA). The relative STD (%) suggested that BPB and BPE show similar binding modes and orientations, in which the phenolic rings were spatially close to HSA binding site. ITC analysis results showed that BPB and BPE were bound to HSA with moderately strong binding affinity through electrostatic interactions and hydrogen bonds. The order of binding affinity of HSA for two test bisphenols is as follows: BPE > BPB. The results of fluorescence competitive experiments using 5-dimethylaminonaphthalene-1-sulfonamide and dansylsarcosine as competitors, combined with molecular docking indicated that both bisphenols are prone to attach to the binding site II in HSA. Spectroscopic results (FT-IR, CD, synchronous and 3D fluorescence spectra) showed that BPB/BPE induces different degrees of microenvironmental and conformational changes to HSA.

Capillary Electrophoresis: Trends and Recent Advances

Abstract: Robert L. C. Voeten,†,‡ Iro K. Ventouri,‡,§ Rob Haselberg,*,† and Govert W. Somsen† †Division of BioAnalytical Chemistry, Department of Chemistry and Pharmaceutical Sciences, Vrije Universiteit Amsterdam, de Boelelaan 1085, 1081 HV Amsterdam, The Netherlands ‡TI-COAST, Science Park 904, 1098 XH Amsterdam, The Netherlands Analytical Chemistry Group, van’t Hoff Institute for Molecular Sciences, University of Amsterdam, Science Park 904, 1098 XH Amsterdam, The Netherlands

On the purported “backbone fluorescence” in protein three-dimensional fluorescence spectra

Abstract: In this study, several proteins (albumin, lysozyme, insulin) and model compounds (Trp, Tyr, homopolypeptides) were used to demonstrate the origin of the fluorescence observed upon their excitation at 220–230 nm. In the last 10 years we have observed a worrying increase in the number of articles claiming that this fluorescence originates from the protein backbone, contrary to the established knowledge that UV protein emission is due to aromatic amino acids only. Overall, our data clearly demonstrate that the observed emission upon excitation at 220–230 nm is due to the excitation of Tyr and/or Trp, with subsequent emission from the lowest excited state (i.e. the same as obtained with 280 nm excitation) in agreement with Kasha's rule. Therefore, this fluorescence peak does not provide any information on backbone conformation, but simply reports on the local environment around the aromatic side chains, just as any traditional protein emission spectrum. The many papers in reputable journals erroneously reporting this peak assignment, contradicting 5 decades of prior knowledge, have led to the creation of a new dogma, where many authors and reviewers now take the purported backbone fluorescence as an established fact. We hope the current paper helps counter this new situation and leads to a reassessment of those papers that make this erroneous claim.

Bioavailability and metabolism of chlorogenic acids (acyl-quinic acids) in humans.

Abstract: Acyl-quinic acids (chlorogenic acids) are produced by many plants, including fruits, vegetables, and herbal remedies, with coffee and mate particularly rich dietary sources. Epidemiological and intervention studies suggest that they can reduce the risk of developing type 2 diabetes and cardiovascular disease. This review addresses their metabolic handling after oral consumption to provide a mechanistic basis to explain their possible effects on health. Intact acyl-quinic acids are absorbed only to a small extent in the small intestine, but the cinnamic acids are efficiently absorbed after hydrolysis by either digestive or microbial enzymes in the colon. Metabolism results in phenolic conjugates in the blood and urine, but varying dependent on the acyl-quinic acid, and subject to significant interperson variability. The balance between hydrogenation and complete β-oxidation of the cinnamic acids, both by liver and gut microbiota, determines the profile of metabolites. Pharmacokinetic data suggest that some metabolites are bound to human serum albumin and/or sequestered in tissues, and some exhibit biological activity in vitro, consistent with proposed protective action in vivo. Significant gaps in the literature include lack of plasma and urinary data for free-living individuals, and pharmacokinetic data for groups who consume coffee or mate at regular short intervals. Data are required for cis isomers. There is a critical need for precise urinary biomarkers of consumption of acyl-quinic acids, accounting for variability in individual metabolism and in beverage composition, thus facilitating better translation of urinary metabolite measurements into accurate coffee consumption data to improve the outcomes of future epidemiological and intervention studies.