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

Yang, Hongqin; Huang, Yanmei; He, Jiawei; Li, Shanshan; Tang, Bin; Li, Hui

doi:10.1016/j.abb.2016.07.016

Cited by 20 publications

(14 citation statements)

References 41 publications

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“…The STD and WaterLOGSY NMR methods are extremely useful techniques to probe and understand weak interactions between small molecules and macromolecules at the molecular level22232425. In the case of STD, the saturation of protein is spread onto the ligand owing to the binding and then the signals of the bound-ligand is identified.…”

Section: Resultsmentioning

confidence: 99%

“…Magnetisation is transferred from water to both free ligands and protein-bound ligands via the protein. The signals allows distinguishing binder and non-binder ligands24. In the following section, STD and WaterLOGSY NMR spectroscopic binding investigations were applied to observe the AAK inhibitor MLN8237–HSA complex system in detail.…”

Section: Resultsmentioning

confidence: 99%

“…Warfarin sodium, an effective chemoprophylaxis agent against thromboembolic disease, is used as a reference spy that preferably binds to site I of HSA27. Ibuprofen, a nonsteroidal anti-inflammatory drug, is recognized as a typical binding spy for site II of HSA24. First, the STD binding experiments at a constant MLN8237/HSA molar ratio of 40:1 (400 μM MLN8237 and 10 μM HSA) were performed as control.…”

Section: Resultsmentioning

confidence: 99%

“…CD is considered as an important tool to elucidate the structure of polypeptides and characterize the secondary structures of proteins2434. As shown in Fig.…”

Section: Resultsmentioning

confidence: 99%

“…The final concentration of HSA in the NMR spectroscopy tube was 10 μM. Competition studies were performed with warfarin sodium and ibuprofen, namely, two known binders of site I and site II of HSA, respectively2427. Different concentrations of warfarin sodium or ibuprofen ([warfarin sodium/ibuprofen]/[MLN8237] = 0.0, 1.2, 3.0) were added into the MLN8237-HSA solution, which was used to analyze the effect of warfarin sodium or ibuprofen on the MLN8237-HSA system, so as to determine the binding site of MLN8237.…”

Section: Methodsmentioning

confidence: 99%

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Domain-specific interactions between MLN8237 and human serum albumin estimated by STD and WaterLOGSY NMR, ITC, spectroscopic, and docking techniques

Yang

Liu

Huang

et al. 2017

Sci Rep

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Alisertib (MLN8237) is an orally administered inhibitor of Aurora A kinase. This small-molecule inhibitor is under clinical or pre-clinical phase for the treatment of advanced malignancies. The present study provides a detailed characterization of the interaction of MLN8237 with a drug transport protein called human serum albumin (HSA). STD and WaterLOGSY nuclear magnetic resonance (NMR)-binding studies were conducted first to confirm the binding of MLN8237 to HSA. In the ligand orientation assay, the binding sites of MLN8237 were validated through two site-specific spy molecules (warfarin sodium and ibuprofen, which are two known site-selective probes) by using STD and WaterLOGSY NMR competition techniques. These competition experiments demonstrate that both spy molecules do not compete with MLN8237 for the specific binding site. The AutoDock-based blind docking study recognizes the hydrophobic subdomain IB of the protein as the probable binding site for MLN8237. Thermodynamic investigations by isothermal titration calorimetry (ITC) reveal that the non-covalent interaction between MLN8237 and HSA (binding constant was approximately 105 M−1) is driven mainly by favorable entropy and unfavorable enthalpy. In addition, synchronous fluorescence, circular dichroism (CD), and 3D fluorescence spectroscopy suggest that MLN8237 may induce conformational changes in HSA.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

“…CD is considered as an important tool to elucidate the structure of polypeptides and characterize the secondary structures of proteins2434. As shown in Fig.…”

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Domain-specific interactions between MLN8237 and human serum albumin estimated by STD and WaterLOGSY NMR, ITC, spectroscopic, and docking techniques

Yang

Liu

Huang

et al. 2017

Sci Rep

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Dissecting the Molecular Properties of Nanoscale Materials Using Nuclear Magnetic Resonance Spectroscopy

Agarwal

Poluri

2022

Spectroscopy and Characterization of Nanomaterials and Novel Materials

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Mechanism understanding of PIKfyve inhibitor YM201636 with human serum albumin: Insights from molecular modeling and multiple spectroscopic techniques

Yang,

Ji,

Wang

et al. 2024

Luminescence

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YM201636 is the potent PIKfyve inhibitor that is being actively investigated for liver cancer efficacy. In this study, computer simulations and experiments were conducted to investigate the interaction mechanism between YM201636 and the transport protein HSA. Results indicated that YM201636 is stably bound between the subdomains IIA and IIIA of HSA, supported by site marker displacement experiments. YM201636 quenched the endogenous fluorescence of HSA by static quenching since a decrease in quenching constants was observed from 7.74 to 2.39 × 104 M−1. UV–vis and time‐resolved fluorescence spectroscopy confirmed the YM201636–HSA complex formation and this binding followed a static mechanism. Thermodynamic parameters ΔG, ΔH, and ΔS obtained negative values suggesting the binding was a spontaneous process driven by Van der Waals interactions and hydrogen binding. Binding constants ranged between 5.71 and 0.33 × 104 M−1, which demonstrated a moderately strong affinity of YM201636 to HSA. CD, synchronous, and 3D fluorescence spectroscopy revealed that YM201636 showed a slight change in secondary structure. The increase of Kapp and a decrease of PSH with YM201636 addition showed that YM201636 changed the surface hydrophobicity of HSA. The research provides reasonable models helping us further understand the transportation and distribution of YM201636 when it absorbs into the blood circulatory system.

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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

Cited by 20 publications

References 41 publications

Domain-specific interactions between MLN8237 and human serum albumin estimated by STD and WaterLOGSY NMR, ITC, spectroscopic, and docking techniques

Domain-specific interactions between MLN8237 and human serum albumin estimated by STD and WaterLOGSY NMR, ITC, spectroscopic, and docking techniques

Dissecting the Molecular Properties of Nanoscale Materials Using Nuclear Magnetic Resonance Spectroscopy

Mechanism understanding of PIKfyve inhibitor YM201636 with human serum albumin: Insights from molecular modeling and multiple spectroscopic techniques

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