title: Interaction of lafutidine in binding to human serum albumin in gastric ulcer therapy: STD-NMR, WaterLOGSY-NMR, NMR relaxation times, Tr-NOESY, molecule docking, and spectroscopic studies.
abstract: In this study, lafutidine (LAF) was used as a model compound to investigate the binding mechanism between antiulcer drugs and human serum albumin (HSA) through various techniques, including STD-NMR, WaterLOGSY-NMR, (1)H NMR relaxation times, tr-NOESY, molecule docking calculation, FT-IR spectroscopy, and CD spectroscopy. The analyses of STD-NMR, which derived relative STD (%) intensities, and WaterLOGSY-NMR, determined that LAF bound to HSA. In particular, the pyridyl group of LAF was in close contact with HSA binding pocket, whereas furyl group had a secondary binding. Competitive STD-NMR and WaterLOGSY-NMR experiments, with warifarin and ibuprofen as site-selective probes, indicated that LAF preferentially bound to site II in the hydrophobic subdomains IIIA of HSA. The bound conformation of LAF at the HSA binding site was further elucidated by transferred NOE effect (tr-NOESY) experiment. Relaxation experiments provided quantitative information about the relationship between the affinity and structure of LAF. The molecule docking simulations conducted with AutoDock and the restraints derived from STD results led to three-dimensional models that were consistent with the NMR spectroscopic data. The presence of hydrophobic forces and hydrogen interactions was also determined. Additionally, FT-IR and CD spectroscopies showed that LAF induced secondary structure changes of HSA.
authors.affiliation: College of Chemical Engineering, Sichuan University, Chengdu 610065, PR China.
authors.forename: Hongqin
authors.initials: H
authors.lastname: Yang
authors.affiliation: College of Chemical Engineering, Sichuan University, Chengdu 610065, PR China.
authors.forename: Yanmei
authors.initials: Y
authors.lastname: Huang
authors.affiliation: College of Chemical Engineering, Sichuan University, Chengdu 610065, PR China.
authors.forename: Jiawei
authors.initials: J
authors.lastname: He
authors.affiliation: College of Chemical Engineering, Sichuan University, Chengdu 610065, PR China.
authors.forename: Shanshan
authors.initials: S
authors.lastname: Li
authors.affiliation: College of Chemical Engineering, Sichuan University, Chengdu 610065, PR China.
authors.forename: Bin
authors.initials: B
authors.lastname: Tang
authors.affiliation: College of Chemical Engineering, Sichuan University, Chengdu 610065, PR China. Electronic address: lihuilab@sina.com.
authors.forename: Hui
authors.initials: H
authors.lastname: Li
mesh_terms: D000081:Acetamides / Q000737:chemistry*; D001665:Binding Sites; D002942:Circular Dichroism; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D062105:Molecular Docking Simulation; D010880:Piperidines / Q000737:chemistry*; D011485:Protein Binding; D000072417:Protein Domains; D017433:Protein Structure, Secondary; D011522:Protons; D011725:Pyridines / Q000737:chemistry*; D012709:Serum Albumin / Q000737:chemistry*; D013053:Spectrophotometry; D017550:Spectroscopy, Fourier Transform Infrared; D013276:Stomach Ulcer / Q000097:blood* / Q000188:drug therapy*; D014859:Warfarin / Q000737:chemistry
chemical_list: D000081:Acetamides; D010880:Piperidines; D011522:Protons; D011725:Pyridines; D012709:Serum Albumin; C076948:lafutidine; D014859:Warfarin
keywords: Conformational changes; Human serum albumin; Lafutidine; Molecule docking; Relaxation experiments and tr-NOESY; STD and WaterLOGSY-NMR