Evaluation of etanercept degradation under oxidative stress and potential protective effects of various amino acids

Lim, Jun Yeul; Kim, Nam Ah; Lim, Dae Gon; Kim, Ki‐Hyun; Hada, Shavron; Jeong, Seong Hoon

doi:10.1016/j.ijpharm.2015.07.018

Cited by 10 publications

(4 citation statements)

References 54 publications

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“…The scavenging of singlet oxygen by histidine was found to be significantly higher than that of tryptophan or methionine [89]. Moreover, histidine is suggested to be protective against oxidative stress in a drug model, reflected in its storage stability [91]. Histidine has been shown to have an inhibitory effect on H 2 O 2 -induced IL-8 secretion in Caco-2 and HT-29 cells [92].…”

Section: Antioxidant Function Of Histidine Against Oxidative Stressmentioning

confidence: 99%

Protective Role of Histidine Supplementation Against Oxidative Stress Damage in the Management of Anemia of Chronic Kidney Disease

et al. 2018

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Anemia is a major health condition associated with chronic kidney disease (CKD). A key underlying cause of this disorder is iron deficiency. Although intravenous iron treatment can be beneficial in correcting CKD-associated anemia, surplus iron can be detrimental and cause complications. Excessive generation of reactive oxygen species (ROS), particularly by mitochondria, leads to tissue oxidation and damage to DNA, proteins, and lipids. Oxidative stress increase in CKD has been further implicated in the pathogenesis of vascular calcification. Iron supplementation leads to the availability of excess free iron that is toxic and generates ROS that is linked, in turn, to inflammation, endothelial dysfunction, and cardiovascular disease. Histidine is indispensable to uremic patients because of the tendency toward negative plasma histidine levels. Histidine-deficient diets predispose healthy subjects to anemia and accentuate anemia in chronic uremic patients. Histidine is essential in globin synthesis and erythropoiesis and has also been implicated in the enhancement of iron absorption from human diets. Studies have found that L-histidine exhibits antioxidant capabilities, such as scavenging free radicals and chelating divalent metal ions, hence the advocacy for its use in improving oxidative stress in CKD. The current review advances and discusses evidence for iron-induced toxicity in CKD and the mechanisms by which histidine exerts cytoprotective functions.

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Section: Antioxidant Function Of Histidine Against Oxidative Stressmentioning

confidence: 99%

Protective Role of Histidine Supplementation Against Oxidative Stress Damage in the Management of Anemia of Chronic Kidney Disease

et al. 2018

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“…Despite the fact of high oxidation rates on some methionine residues, a recent study found that oxidation has no influence on the bioactivity of etanercept [15]. However, tracking the methionine oxidation is of importance in comparability studies since it can serve as the protectant against oxidative stress [16] and can protect the protein from degradation. Our data implied that methionine 272 which was the most sensitive methionine for oxidation is located in the CH2 domain and indicate that this region is highly prone to modifications such as amidation, deamidation and oxidation.…”

Section: Discussionmentioning

confidence: 99%

“…Rather than the comparability studies that compared and analyzed the structure and function of a biosimilar with the originator, several publications can also be found which evaluate the different properties of etanercept in detail. These studies included the evaluation of glycosylation sites, composition or functional effects [8,11,12,13,14], analysis of the oxidation or deamidation sites and their effects on function and structure [15,16] as well as disulfide bonds and their functional effects [17]. In this study, the individual mass spectrometric measurements were examined and compared.…”

Section: Introductionmentioning

confidence: 99%

Structural and In Vitro Functional Comparability Analysis of Altebrel™, a Proposed Etanercept Biosimilar: Focus on Primary Sequence and Glycosylation

et al. 2019

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The demand for reliable comparability studies of biosimilars grows with their increased market share. These studies focus on physicochemical, structural, functional and clinical properties to ensure that a biosimilar has no significant differences to the originator product and can be released into the market without extensive clinical trials. In the current study, Enbrel® (etanercept, the originator) and Altebrel™ (the proposed biosimilar) underwent direct comparison. “Bottom-up” mass spectrometric analysis was used for primary sequence analysis, evaluation of N/O-glycosylation sites and quantification of methionine oxidation. N/O-glycans were analyzed after permethylation derivatization and the effect of N-glycans on in-vitro functionality of etanercept was assayed. Three enzyme peptide mapping resulted in complete identification of the primary structure. It was confirmed that total ion chromatograms are valuable datasets for the analysis of the primary structure of biodrugs. New N/O-glycan structures were identified and all the N-glycans were quantified. Finally, investigation of the functional properties of N-deglycosylated and non-modified etanercept samples using surface plasmon resonance analysis and in-vitro bioassay showed that N-glycosylation has no significant effect on its in-vitro functionality. Analysis of etanercept and its biosimilar, revealed a high similarity in terms of glycosylation, primary structure and in-vitro functionality.

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“…Besides being the building block for proteins, amino acids are widely utilised as excipients in freeze-and spraydrying (32), as stabilising additives (32)(33)(34), as osmolytes (35) in liquid protein-based drug formulations or as stabiliser in crystalline formulations (36). In liquid protein formulations, hydrophobic and acidic hydrophilic amino acids have been used to thermally stabilise lysozyme (37) and pig heart mitochondrial malate dehydrogenase (32) respectively, while methionine and histidine increases the stability against oxidative stress to enhance the long-term storage capability (32,38,39). Furthermore, amino acids, especially arginine, have been used to prevent protein denaturation (32,34,40).…”

Section: Introductionmentioning

confidence: 99%

Enhancing the crystallisation of insulin using amino acids as soft-templates to control nucleation

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Heng

2021

CrystEngComm

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Evaluation of etanercept degradation under oxidative stress and potential protective effects of various amino acids

Cited by 10 publications

References 54 publications

Protective Role of Histidine Supplementation Against Oxidative Stress Damage in the Management of Anemia of Chronic Kidney Disease

Protective Role of Histidine Supplementation Against Oxidative Stress Damage in the Management of Anemia of Chronic Kidney Disease

Structural and In Vitro Functional Comparability Analysis of Altebrel™, a Proposed Etanercept Biosimilar: Focus on Primary Sequence and Glycosylation

Enhancing the crystallisation of insulin using amino acids as soft-templates to control nucleation

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