title: Exploring the binding of 4-thiothymidine with human serum albumin by spectroscopy, atomic force microscopy, and molecular modeling methods.
abstract: The interaction of 4-thiothymidine (S(4)TdR) with human serum albumin (HSA) was studied by equilibrium dialysis under normal physiological conditions. In this work, the mechanism of the interaction between S(4)TdR and human serum albumin (HSA) was exploited by fluorescence, UV, CD circular, and SERS spectroscopic. Fluorescence and UV spectroscopy suggest that HSA intensities are significantly decreased when adding S(4)TdR to HAS, and the quenching mechanism of the fluorescence is static. Also, the ΔG, ΔH, and ΔS values across temperature indicated that hydrophobic interaction was the predominant binding force. The CD circular results show that there is little change in the secondary structure of HSA except the environment of amino acid changes when adding S(4)TdR to HSA. The surface-enhanced Raman scattering (SERS) shows that the interaction between S(4)TdR and HSA can be achieved through different binding sites which are probably located in the II A and III A hydrophobic pockets of HSA which correspond to Sudlow's I and II binding sites. In addition, the molecular modeling displays that S(4)TdR-HSA complex is stabilized by hydrophobic forces, which result from amino acid residues. The atomic force microscopy results revealed that the single HSA molecular dimensions were larger after interaction of 4-thiothymidine. This work would be useful to understand the state of the transportation, distribution, and metabolism of the anticancer drugs in the human body, and it could provide a useful biochemistry parameter for the development of new anti-cancer drugs and research of pharmacology mechanisms.
authors.affiliation: MOE Key laboratory of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou 510631, China.
authors.forename: Juling
authors.initials: J
authors.lastname: Zhang
authors.affiliation: MOE Key laboratory of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou 510631, China. Electronic address: guhm@scnu.edu.cn.
authors.forename: Huaimin
authors.initials: H
authors.lastname: Gu
authors.affiliation: College of Environment and Chemical Engineering, Dalian University, Dalian, Liaoning 116622, China.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Zhang
mesh_terms: D001665:Binding Sites; D002942:Circular Dichroism; D006801:Humans; D018625:Microscopy, Atomic Force; D008958:Models, Molecular; D012709:Serum Albumin / Q000737:chemistry*; D013050:Spectrometry, Fluorescence; D013056:Spectrophotometry, Ultraviolet; D013059:Spectrum Analysis, Raman; D013936:Thymidine / Q000031:analogs & derivatives* / Q000737:chemistry
chemical_list: C414668:4-thiothymidine; D012709:Serum Albumin; D013936:Thymidine
keywords: Atomic force microscopy; Human serum albumin; Molecular modeling; S(4)TdR; SERS