Furosemide Derails Human Lysozyme Fibrillation by Interacting with Aggregation Hot Spots: A Biophysical Comprehension.

Kidney-associated human lysozyme amyloidosis leads to renal impairments;thus, patients are often prescribed furosemide. Based on this fact, the effect of furosemide on induced human lysozyme fibrillation, , is evaluated by spectroscopic, calorimetric, computational, and cellular-based assays/methods. Results show that furosemide increases the lag phase and decreases the apparent rate of aggregation of human lysozyme, thereby decelerating the nucleation phase and amyloid fibril formation, as confirmed by the decrease in the level of Thioflavin-T fluorescence.

Biophysical insight into anti-amyloidogenic nature of novel ionic Co(II)(phen)(HO)][glycinate] chemotherapeutic drug candidate against human lysozyme aggregation.

In the recent past, there has been an ever-increasing interest in the search for metal-based therapeutic drug candidates for protein misfolding disorders (PMDs) particularly neurodegenerative disorders such as Alzheimer's, Parkinson's, Prion's diseases, and amyotrophic lateral sclerosis. Also, different amyloidogenic variants of human lysozyme (HL) are involved in hereditary systemic amyloidosis. Metallo-therapeutic agents are extensively studied as antitumor agents, however, they are relatively unexplored for the treatment of non-neuropathic amyloidoses.

Description of a new species of Probrachista (Hymenoptera: Chalcidoidea: Trichogrammatidae) from Ladakh, India.

The present paper deals with the description of a new species Probrachista turtukensis Manhas, Anis & Khan sp. nov, from the region of Ladakh, India. A key to world species of the genus Probrachista Viggiani, is also given.

Mechanistic insight into inhibition of amyloid fibrillation of human serum albumin by Vildagliptin.

Protein aggregation leads to several human pathologies such as Alzheimer's disease (AD), type 2 diabetes (T2D), Parkinson's disease (PD), etc. Due to the overlap in the mechanisms of type 2 diabetes and brain disorders, common effective pharmacological interventions to treat both T2D and AD is under extensive research. Therefore, major aim of research is to repurpose already established treatment of diabetes to cure AD as well.

Mechanistic In Vitro Dissection of the Inhibition of Amyloid Fibrillation by -Acetylneuraminic Acid: Plausible Implication in Therapeutics for Neurodegenerative Disorders.

A variety of neurodegenerative disorders including Parkinson's disease are due to fibrillation in amyloidogenic proteins. The development of therapeutics for these disorders is a topic of extensive research as effective treatments are still unavailable. The present study establishes that -acetylneuraminic acid (Neu5ac) inhibits the amyloid fibrillation of hen egg-white lysozyme (HEWL) and α-synuclein (SYN), as observed using various biophysical techniques and cellular assays.

Probing the Nongeneralized Amyloid Inhibitory Mechanism of Hydrophobic Chaperone.

Increasing prevalence of protein misfolding disorders urges the search for effective therapies. Although several antiaggregation molecules have been identified, their molecular process of aggregation and clinical trials are underway. The present study is focused on the mechanism through which phenyl butyrate (PB), a chemical chaperone, triggers inhibition of human serum albumin (HSA) fibrillation.

A biophysical insight into structural and functional state of human serum albumin in uremia mimic milieu.

In chronic kidney diseases (CKD), uremic toxins accumulate in the blood plasma of patients and interact with human serum albumin (HSA) and thus impaired its role as carrier protein. Present study shows in vitro effect of carboxy-4-methyl-5-propyl-2-furanpropanoic acid (CMPF), indoxyl sulfate (IS), indole-3 acetic acid (IAA), and hippuric acid (HA) with human serum albumin (HSA) at pathological concentrations. HSA bind with CMPF, IS and IAA at both of its binding sites with high affinity (order of 10 to 10 M) and low affinity (order of 10 to 10 M).

Biophysical insights into the interaction of clofazimine with human alpha 1-acid glycoprotein: a multitechnique approach.

Alpha1-acid glycoprotein (AAG) is a major acute phase protein of human plasma. Binding of clofazimine to AAG is investigated using optical spectroscopy and molecular docking tools. We found significant quenching of intrinsic fluorescence of AAG upon the binding of clofazimine, binding mode is static with binding constant of 3.

Interaction of catecholamine precursor l-Dopa with lysozyme: A biophysical insight.

The current study comprises of an inclusive biophysical study, enlightening the binding of L-3, 4-dihydroxyphenylalanine (l-Dopa) with human lysozyme (HL) and hen egg white lysozyme (HEWL). Spectroscopic and molecular docking tools have been utilized to study the interaction of l-Dopa with both HL and HEWL. Spectrofluorimetric measurements exhibited that l-Dopa quenched the HL and HEWL intrinsic fluorescence.

Deciphering the enhanced inhibitory, disaggregating and cytoprotective potential of promethazine towards amyloid fibrillation.

Increasing evidence proposed that amyloid deposition by proteins play a crucial role in an array of neurotoxic and degenerative disorders like Parkinson's disease, systemic amyloidosis etc, that could be controlled by anti-aggregation methodologies which either inhibit or disaggregate such toxic aggregates. The present work targets the amyloid inhibiting and disaggregating potential of promethazine (PRM) against human insulin (HI) and human lysozyme (HL) fibrillogenesis. Biophysical techniques like Rayleigh scattering measurements (RLS), Thioflavin T (ThT) and 8-Anilinonaphthalene-1-sulfonic acid (ANS) fluorescence measurement, circular dichroism (CD) and dynamic light scattering (DLS) measurements illustrated the inhibitory action of PRM.

Anti-Parkinsonian L-Dopa can also act as anti-systemic amyloidosis-A mechanistic exploration.

In spite of the fact that amyloid related neurodegenerative illnesses and non-neuropathic systemic amyloidosis have allured the research endeavors, as no cure has been announced yet apart from symptomatic treatment. Therapeutic agents which can reduce or disaggregate those toxic oligomers and fibrillar species have been studied with more compounds are on their way. The current research work describes comprehensive biophysical, computational and microscopic studies which reveal that L-3, 4-dihydroxyphenylalanine (L-Dopa) have indisputable efficacy to hinder the heat induced amyloid fibrillation of the human lysozyme (HL) and also preserve the fibril disaggregating potential.

A multitechnique approach to probe the interaction of a therapeutic tyrosine kinase inhibitor nintedanib and bovine serum albumin.

Drug and protein interaction provides a structural guideline in the rational drug designing and in the synthesis of new and improved drugs with greater efficacy. We have examined here the interaction tendency and mechanism of nintedanib (NTB), an anticancer drug (tyrosine kinase inhibitor) with bovine serum albumin (BSA), by spectroscopic techniques. The decline in Stern-Volmer quenching constants and binding constant with the temperature rise suggests that BSA forms a complex with NTB.

Interaction of anticancer drug clofarabine with human serum albumin and human α-1 acid glycoprotein. Spectroscopic and molecular docking approach.

The binding interaction between clofarabine, an important anticancer drug and two important carrier proteins found abundantly in human plasma, Human Serum Albumin (HSA) and α-1 acid glycoprotein (AAG) was investigated by spectroscopic and molecular modeling methods. The results obtained from fluorescence quenching experiments demonstrated that the fluorescence intensity of HSA and AAG is quenched by clofarabine and the static mode of fluorescence quenching is operative. UV-vis spectroscopy deciphered the formation of ground state complex between anticancer drug and the two studied proteins.

Repositioning nordihydroguaiaretic acid as a potent inhibitor of systemic amyloidosis and associated cellular toxicity.

Although the cure of amyloid related neurodegenerative diseases, non-neuropathic amyloidogenic diseases and non-neuropathic systemic amyloidosis are appealing energetic research attempts, beneficial medication is still to be discovered. There is a need to explore intensely stable therapeutic compounds, potent enough to restrict, disrupt or wipe out such toxic aggregates. We had performed a comprehensive biophysical, computational and cell based assay, that shows Nordihydroguaiaretic acid (NA) not only significantly inhibits heat induced hen egg white lysozyme (HEWL) fibrillation but also disaggregates preformed HEWL fibrils and reduces the cytoxicity of amyloid fibrils as well as disaggregated fibrillar species.

Fibrillogenesis of human serum albumin in the presence of levodopa - spectroscopic, calorimetric and microscopic studies.

Studying amyloid associated neurodegenerative diseases is an active area of research. Cure for these diseases are still to be discovered. In the present study we have performed comprehensive biophysical and computational experiments showing levodopa not only significantly inhibits heat induced fibrillization of human serum albumin but also disaggregates preformed fibrils.

Biophysical insights into the interaction of hen egg white lysozyme with therapeutic dye clofazimine: modulation of activity and SDS induced aggregation of model protein.

The present study details the binding process of clofazimine to hen egg white lysozyme (HEWL) using spectroscopy, dynamic light scattering, transmission electron microscopy (TEM), and molecular docking techniques. Clofazimine binds to the protein with binding constant (K) in the order of 1.57 × 10 at 298 K.

A Comprehensive Spectroscopic and Computational Investigation to Probe the Interaction of Antineoplastic Drug Nordihydroguaiaretic Acid with Serum Albumins.

Exogenous drugs that are used as antidote against chemotheray, inflammation or viral infection, gets absorbed and interacts reversibly to the major serum transport protein i.e. albumins, upon entering the circulatory system.

Insight into the interaction of antitubercular and anticancer compound clofazimine with human serum albumin: spectroscopy and molecular modelling.

The binding of clofazimine to human serum albumin (HSA) was investigated by applying optical spectroscopy and molecular docking methods. Fluorescence quenching data revealed that clofazimine binds to protein with binding constant in the order of 10 M, and with the increase in temperature, Stern-Volmer quenching constants gradually decreased indicating quenching mode to be static. The UV-visible spectra showed increase in absorbance upon interaction of HSA with clofazimine which further reveals formation of the drug-albumin complex.

Unraveling Comparative Anti-Amyloidogenic Behavior of Pyrazinamide and D-Cycloserine: A Mechanistic Biophysical Insight.

Amyloid fibril formation by proteins leads to variety of degenerative disorders called amyloidosis. While these disorders are topic of extensive research, effective treatments are still unavailable. Thus in present study, two anti-tuberculosis drugs, i.

Thermal induced unfolding of human serum albumin isomers: assigning residual α helices to domain II.

In this study we have investigated the heat induced denaturation of HSA by utilizing spectroscopic approaches including fluorescence and circular dichroism. Thermal denaturation of N isomer (domains I-III remain intact), B isomer (loss of helical structure of interdomain contacts) and I state (domain II intact) was found to be co-operative processes while for F isomer domains unfold non-cooperatively. These finding pointed out that during N-F transition, HSA suffers more structural alterations which are not localized only to domain III.

pH-dependent differential interacting mechanisms of sodium dodecyl sulfate with bovine serum fetuin: a biophysical insight.

Sodium dodecyl sulfate (SDS)-glycoprotein interaction serves as a model for a biological membrane. To get mechanistic insight into the interaction of SDS and glycoprotein, the effect of SDS on bovine serum fetuin (BSF) was studied in subcritical micellar concentrations at pH 7.4 and pH 2 using multiple approaches.