Morphological changes in human serum albumin in the presence of cationic amphiphilic drugs

Yaseen, Zahid; Aswal, Vinod K.; Zhou, Xuan; Kabir-ud-Din, †; Haider, Shozeb

doi:10.1039/c7nj02591b

Cited by 9 publications

(5 citation statements)

References 43 publications

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“…HSA folds into three homologous domains (I, II, and III) and each domain is formed by two subdomains (A and B). HSA is the dominant protein in adult plasma (~40 mg mL −1 [ 69 ]) and is reported to bind 75–85% (9–14 μM) of the Zn 2+ circulating in the blood [ 70 ]. This makes HSA the major regulator of Zn 2+ “speciation” in the plasma, where speciation refers to the state in which Zn 2+ is present (bound or unbound; and, if bound, to which partner molecule(s)).…”

Section: Control Of Plasma Zn 2+ Availability and The Impact Of Nefasmentioning

confidence: 99%

The Interplay between Non-Esterified Fatty Acids and Plasma Zinc and Its Influence on Thrombotic Risk in Obesity and Type 2 Diabetes

Hierons

Marsh

et al. 2021

IJMS

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Thrombosis is a major comorbidity of obesity and type-2 diabetes mellitus (T2DM). Despite the development of numerous effective treatments and preventative strategies to address thrombotic disease in such individuals, the incidence of thrombotic complications remains high. This suggests that not all the pathophysiological mechanisms underlying these events have been identified or targeted. Non-esterified fatty acids (NEFAs) are increasingly regarded as a nexus between obesity, insulin resistance, and vascular disease. Notably, plasma NEFA levels are consistently elevated in obesity and T2DM and may impact hemostasis in several ways. A potentially unrecognized route of NEFA-mediated thrombotic activity is their ability to disturb Zn2+ speciation in the plasma. Zn2+ is a potent regulator of coagulation and its availability in the plasma is monitored carefully through buffering by human serum albumin (HSA). The binding of long-chain NEFAs such as palmitate and stearate, however, trigger a conformational change in HSA that reduces its ability to bind Zn2+, thus increasing the ion’s availability to bind and activate coagulation proteins. NEFA-mediated perturbation of HSA-Zn2+ binding is thus predicted to contribute to the prothrombotic milieu in obesity and T2DM, representing a novel targetable disease mechanism in these disorders.

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Section: Control Of Plasma Zn 2+ Availability and The Impact Of Nefasmentioning

confidence: 99%

The Interplay between Non-Esterified Fatty Acids and Plasma Zinc and Its Influence on Thrombotic Risk in Obesity and Type 2 Diabetes

Hierons

Marsh

et al. 2021

IJMS

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“…The culmination of so many structures can be attributed to the property of HSA, which is able to bind and transport a number of different ligands. Due to its transport function, several groups have studied the interactions of clinically important drugs and small molecules with HSA. , It had a tremendous impact on the clinical studies and led to a better understanding of the pharmacokinetics of drugs such as axitinib and doxorubicin …”

Section: Introductionmentioning

confidence: 99%

“…Due to its transport function, several groups have studied the interactions of clinically important drugs and small molecules with HSA. 31,32 It had a tremendous impact on the clinical studies and led to a better understanding of the pharmacokinetics of drugs such as axitinib 33 and doxorubicin. 34 The use of NPs in drug delivery will be feasible only when HSA−NP interaction does not change the protein conformation.…”

Section: Introductionmentioning

confidence: 99%

Computational Analysis of the Silver Nanoparticle–Human Serum Albumin Complex

Hazarika

Jha

2019

ACS Omega

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Drug delivery in excess concentrations and at not-specified sites inside the human body adversely affects the body and gives rise to other diseases. Several methods have been developed to deliver the drugs in required amounts and at specific targets. Nanoparticle-mediated drug delivery is one such approach and has gained success at primary levels. The effect of nanoparticles on the human body needs important apprehension, and it has been unraveled by assessing the protein–nanoparticle interactions. Here, we have measured the impact of silver nanoparticles (AgNPs) on the human serum albumin (HSA) structure and function with the help of all-atom molecular dynamics simulations (MDS). HSA is a transport protein, and any change in the structure may obstruct its function. The post MD analyses showed that the NP interacts with HSA and the conjugated system got stabilized with time evolution of trajectories. The present investigation confirms that the AgNP interacts with HSA without affecting its tertiary and secondary structures and in turn the protein function as well. AgNP application is recommended in transporting conjugated drug molecules as it has no adverse effect on serum proteins. Since HSA is present in the circulatory system, it may open various applications of AgNPs in the biomedical field.

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“…10 Its special spherical structure domain and helical structure show the numerous hydrophobic cavities in the HSA molecules, which can integrate various small molecules. 11 HSA is a major carrier of many endogenous and exogenous compounds, such as fatty acids, hormones, tryptophan (Trp), and metal cations. HSA binds to these compounds to form a complex, which is transported by blood circulation to its targets.…”

Section: Introductionmentioning

confidence: 99%

Characterization of interactions of montelukast sodium with human serum albumin: multi-spectroscopic techniques and computer simulation studies

et al. 2022

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Morphological changes in human serum albumin in the presence of cationic amphiphilic drugs

Abstract: Binding of cationic amphiphilic drugs results in unfolding of human serum albumin.

Cited by 9 publications

References 43 publications

The Interplay between Non-Esterified Fatty Acids and Plasma Zinc and Its Influence on Thrombotic Risk in Obesity and Type 2 Diabetes

The Interplay between Non-Esterified Fatty Acids and Plasma Zinc and Its Influence on Thrombotic Risk in Obesity and Type 2 Diabetes

Computational Analysis of the Silver Nanoparticle–Human Serum Albumin Complex

Characterization of interactions of montelukast sodium with human serum albumin: multi-spectroscopic techniques and computer simulation studies

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