Abstract
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 104 M−1 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.
Highlights
The physiological functions of our body are governed by various factors where many essential elements play a vital role
A concentration-dependent quenching of the intrinsic fluorescence of human transferrin (hTf) by Rivastigmine tartrate (RT) was observed upon spectral monitoring of the fluorescence intensity of the hTf–RT interaction (Figure 1)
RT-hTf binding: Calorimetric responses owing to consecutive injections of in the ample cell with hTf are depicted in upper half whilst the the owing to consecutive injections of RT in the ample cell with hTf are depicted in upper half whilst lower panel shows integrated heats of interactions as a function of the [RT]/[hTf] molar ratio
Summary
The physiological functions of our body are governed by various factors where many essential elements play a vital role. Maintaining proper levels of these elements is very important and the homeostasis is controlled through highly regulated mechanisms of uptake, storage, and secretion [1] This disrupted homeostasis is implicated in many disorders ranging from Alzheimer’s (AD), Parkinson’s (PD), and Huntington’s (HD) diseases to amyotrophic lateral sclerosis (ALS) [2,3,4,5]. 4 kDa peptides of ~40–42 amino acids and are key players in Alzheimer’s disease [15] The importance of this disorder can take note from the fact that, globally, it affects nearly 40 million people coupled with a well-being budget of about $820 billion per year [16,17]. This study employed fluorescence spectroscopy observations coupled with molecular docking studies for better insight into the RT–hTf interaction
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