Unraveling Binding Mechanism of Alzheimer’s Drug Rivastigmine Tartrate with Human Transferrin: Molecular Docking and Multi-Spectroscopic Approach towards Neurodegenerative Diseases
Studying drug−protein interactions has gained significant attention lately, and this is because the majority of drugs interact with proteins, thereby altering their structure and, moreover, their functionality. Rivastigmine tartrate (RT) is a drug that is in use for mild to moderate Alzhei...
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doaj-e52df3604f66439dae06618f12dd907c2020-11-25T02:01:02ZengMDPI AGBiomolecules2218-273X2019-09-019949510.3390/biom9090495biom9090495Unraveling Binding Mechanism of Alzheimer’s Drug Rivastigmine Tartrate with Human Transferrin: Molecular Docking and Multi-Spectroscopic Approach towards Neurodegenerative DiseasesAnas Shamsi0Taj Mohammad1Mohd Shahnawaz Khan2Moyad Shahwan3Fohad Mabood Husain4Md. Tabish Rehman5Md. Imtaiyaz Hassan6Faizan Ahmad7Asimul Islam8Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, New Delhi 110025, IndiaCentre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, New Delhi 110025, IndiaDepartment of Biochemistry, College of Sciences, King Saud University, Riyadh 11451, Saudi ArabiaCollege of Pharmacy & Health sciences, Ajman University, Ajman, UAEDepartment of Food Science and Nutrition, Faculty of Food and Agricultural Sciences, King Saud University, Riyadh 11451, Saudi ArabiaDepartment of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh 11451, Saudi ArabiaCentre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, New Delhi 110025, IndiaCentre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, New Delhi 110025, IndiaCentre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, New Delhi 110025, IndiaStudying drug−protein interactions has gained significant attention lately, and this is because the majority of drugs interact with proteins, thereby altering their structure and, moreover, their functionality. Rivastigmine tartrate (RT) is a drug that is in use for mild to moderate Alzheimer therapy. This study was targeted to characterize the interaction between human transferrin (hTf) and RT by employing spectroscopy, isothermal titration calorimetry (ITC), and molecular docking studies. Experimental results of fluorescence quenching of hTf induced by RT implied the formation of a static complex between hTf and RT. Further elucidation of the observed fluorescence data retorting Stern−Volmer and modified Stern−Volmer resulted in binding constants for hTf−RT complex of the order 10<sup>4</sup> M<sup>−1</sup> over the studied temperatures. Thermodynamic parameters of hTf−RT interaction were elucidated further by employing these obtained binding constant values. It was quite evident from obtained thermodynamic attributes that RT spontaneously binds to hTf with a postulated existence of hydrogen bonding or Van der Waals forces. Further, Circular dichroism spectroscopy (CD) also confirmed RT−hTf complex formation owing to upward movement of CD spectra in the presence of RT. ITC profiles advocated the existence of reaction to be spontaneous. Moreover, molecular docking further revealed that the important residues play a pivotal role in RT−hTf interaction. The findings of this study can be of a significant benefit to the drug-designing industry in this disease-prone era.https://www.mdpi.com/2218-273X/9/9/495human transferrinrivastigmine tartratespectroscopymolecular dockingisotheral titration calorimetryAlzheimer’s diseaseneurodegenerative disorders |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Anas Shamsi Taj Mohammad Mohd Shahnawaz Khan Moyad Shahwan Fohad Mabood Husain Md. Tabish Rehman Md. Imtaiyaz Hassan Faizan Ahmad Asimul Islam |
spellingShingle |
Anas Shamsi Taj Mohammad Mohd Shahnawaz Khan Moyad Shahwan Fohad Mabood Husain Md. Tabish Rehman Md. Imtaiyaz Hassan Faizan Ahmad Asimul Islam Unraveling Binding Mechanism of Alzheimer’s Drug Rivastigmine Tartrate with Human Transferrin: Molecular Docking and Multi-Spectroscopic Approach towards Neurodegenerative Diseases Biomolecules human transferrin rivastigmine tartrate spectroscopy molecular docking isotheral titration calorimetry Alzheimer’s disease neurodegenerative disorders |
author_facet |
Anas Shamsi Taj Mohammad Mohd Shahnawaz Khan Moyad Shahwan Fohad Mabood Husain Md. Tabish Rehman Md. Imtaiyaz Hassan Faizan Ahmad Asimul Islam |
author_sort |
Anas Shamsi |
title |
Unraveling Binding Mechanism of Alzheimer’s Drug Rivastigmine Tartrate with Human Transferrin: Molecular Docking and Multi-Spectroscopic Approach towards Neurodegenerative Diseases |
title_short |
Unraveling Binding Mechanism of Alzheimer’s Drug Rivastigmine Tartrate with Human Transferrin: Molecular Docking and Multi-Spectroscopic Approach towards Neurodegenerative Diseases |
title_full |
Unraveling Binding Mechanism of Alzheimer’s Drug Rivastigmine Tartrate with Human Transferrin: Molecular Docking and Multi-Spectroscopic Approach towards Neurodegenerative Diseases |
title_fullStr |
Unraveling Binding Mechanism of Alzheimer’s Drug Rivastigmine Tartrate with Human Transferrin: Molecular Docking and Multi-Spectroscopic Approach towards Neurodegenerative Diseases |
title_full_unstemmed |
Unraveling Binding Mechanism of Alzheimer’s Drug Rivastigmine Tartrate with Human Transferrin: Molecular Docking and Multi-Spectroscopic Approach towards Neurodegenerative Diseases |
title_sort |
unraveling binding mechanism of alzheimer’s drug rivastigmine tartrate with human transferrin: molecular docking and multi-spectroscopic approach towards neurodegenerative diseases |
publisher |
MDPI AG |
series |
Biomolecules |
issn |
2218-273X |
publishDate |
2019-09-01 |
description |
Studying drug−protein interactions has gained significant attention lately, and this is because the majority of drugs interact with proteins, thereby altering their structure and, moreover, their functionality. Rivastigmine tartrate (RT) is a drug that is in use for mild to moderate Alzheimer therapy. This study was targeted to characterize the interaction between human transferrin (hTf) and RT by employing spectroscopy, isothermal titration calorimetry (ITC), and molecular docking studies. Experimental results of fluorescence quenching of hTf induced by RT implied the formation of a static complex between hTf and RT. Further elucidation of the observed fluorescence data retorting Stern−Volmer and modified Stern−Volmer resulted in binding constants for hTf−RT complex of the order 10<sup>4</sup> M<sup>−1</sup> over the studied temperatures. Thermodynamic parameters of hTf−RT interaction were elucidated further by employing these obtained binding constant values. It was quite evident from obtained thermodynamic attributes that RT spontaneously binds to hTf with a postulated existence of hydrogen bonding or Van der Waals forces. Further, Circular dichroism spectroscopy (CD) also confirmed RT−hTf complex formation owing to upward movement of CD spectra in the presence of RT. ITC profiles advocated the existence of reaction to be spontaneous. Moreover, molecular docking further revealed that the important residues play a pivotal role in RT−hTf interaction. The findings of this study can be of a significant benefit to the drug-designing industry in this disease-prone era. |
topic |
human transferrin rivastigmine tartrate spectroscopy molecular docking isotheral titration calorimetry Alzheimer’s disease neurodegenerative disorders |
url |
https://www.mdpi.com/2218-273X/9/9/495 |
work_keys_str_mv |
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