Investigation of Non-Enzymatic Glycosylation of Human Serum Albumin Using Ion Trap-Time of Flight Mass Spectrometry

Bai, Xue; Wang, Zhangjie; Huang, Chengcai; Wang, Zhe

doi:10.3390/molecules17088782

Cited by 31 publications

(42 citation statements)

References 29 publications

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“…2c). Hydrolysis kinetics of labelled liraglutide was assessed by measuring the 19 F NMR signal for liraglutide and trifluoroacetate over a sixty-hour duration. Thereby, a time limitation for experiment was fixed at 6 hours, corresponding to the beginning of the significant detectable hydrolysis of labelled liraglutide into liraglutide and trifluoroacetate ( Figure S1, see supplementary data).…”

Section: Resultsmentioning

confidence: 99%

“…Therefore, in patients with high glycation ratio evaluated according to HbA1c levels (higher than 7%), the action of liraglutide may be compromised. For diabetic patients, the level of glycated albumin can be two-to three-fold higher compared to in healthy people (19,20). This increased glycation rate of albumin could explain the difference in efficiency of fattyacid grafted drugs observed in some patients suffering from advanced forms of diabetes (21).…”

Section: Albumin-liraglutide Interactionmentioning

confidence: 97%

“…19 F NMR is one of the best validated techniques for monitoring ligand-protein interactions (22)(23)(24)(25)(26)(27). This method has already been used to study the binding of various drugs to albumin, either using naturally fluorinated drugs or by competition with fluorinated spy molecules (24,(37)(38)(39)(40)(41)(42).…”

Section: Discussionmentioning

confidence: 99%

“…This increased glycation rate of albumin could explain the difference in efficiency of fattyacid grafted drugs observed in some patients suffering from advanced forms of diabetes (21). In this work, 19 F NMR transverse relaxation time experiments were used to investigate how albumin glycation influences its binding properties to liraglutide. Fluorine NMR is one of the best suited techniques for probing protein-ligand interactions (22)(23)(24)(25)(26)(27).…”

Section: Albumin-liraglutide Interactionmentioning

confidence: 99%

“…Our objective in this study was to assess the impact of human serum albumin (HSA) glycation on liraglutide affinity. Using fluorine labeling of the drug and 19 F NMR, we determined HSA affinity for liraglutide in two glycated albumin models. We either glycated HSA in vitro by incubation with glucose (G25-or G100-HSA) or methylglyoxal (MGO-HSA) or purified in vivo glycated HSA from the plasma of diabetic patients with poor glycemic control.…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Glycation of human serum albumin impairs binding to the glucagon-like peptide-1 analogue liraglutide

Soudahome

Catan

Giraud

et al. 2018

Journal of Biological Chemistry

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Section: Resultsmentioning

confidence: 99%

Section: Albumin-liraglutide Interactionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

Section: Albumin-liraglutide Interactionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Glycation of human serum albumin impairs binding to the glucagon-like peptide-1 analogue liraglutide

Soudahome

Catan

Giraud

et al. 2018

Journal of Biological Chemistry

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Vitamin D prevents glycation of proteins: an in vitro study

2016

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Human serum albumin (HSA) is an important protein involved in the transport of hormones, fatty acids, drugs, and other macromolecules. Under hyperglycemic conditions, this molecule undergoes irreversible modification that affects its structure and function. In this study, we explored the effect of two forms of vitamin D, a nutraceutical, on glycation modification in HSA. The protein was incubated with a physiologically high concentration of glucose in the presence of vitamin D metabolites. After 21 days, samples were tested for secondary structural changes, side chain modification, and the presence of advanced glycation end products. Vitamin D metabolites could reduce glycation modification, albeit only to a small extent. Interaction studies reveal that Vitamin D interaction with HSA can prevent protein glycation.Keywords: calcitriol; glycation; protein Type 2 Diabetes is a global health issue growing at an unprecedented rate. The disease accounts for 90% of diabetes cases worldwide and is characterized by defects in glucose metabolism [1]. Persistently high blood glucose concentration encountered in diabetes often initiates Maillard reaction which causes nonenzymatic glycation of proteins and yields a plethora of reactive compounds called advanced glycation end products (AGEs) [2].Modification of protein structure and function by AGEs is consistent with the progression of diabetic complications and correlates positively with the severity of conditions like retinopathy, neuropathy, and nephropathy [3]. Once initiated, AGEs formation continues throughout the lifespan of proteins, and cannot be reversed by normalizing hyperglycemia [2,4].Human serum albumin (HSA) frequently undergoes Maillard reaction to from covalently cross-linked composites [3]. In normal adults, 6-10% of lysine chains are modified by nonenzymatic glycation, however, this number increases by 2-3 folds in individuals suffering from diabetes [5]. This may interfere with HSA function [5]. Since HSA is involved in the transportation of several moieties: nutrients, steroids, and a wide variety of drugs this can have detrimental physiological effects [6].Research suggests that vitamin D is involved in controlling AGE-associated damage in both diabetes and heart disorders [7]. Vitamin D is a fat-soluble micronutrient which is produced in the body by UV irradiation of a precursor steroid stored in the skin. The functionally active form of vitamin D, calcitriol, has a wide array of health implications [8]. Multiple studies have demonstrated its ability in limiting oxidative damage and regulating the status of a potent cellular antioxidant-reduced glutathione (GSH) [7]. Vitamin D deficiency is thought to be a risk factor for the development of diabetes; Low vitamin D status is associated with increased insulin resistance, glycated hemoglobin (HbA1c), and AGE formation [9][10][11]. Previous reports have correlated low circulating concentrations of vitamin D with increased risk of diabetic macrovascular and microvascular complications: mainly nephropathy a...

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Site‐Selective Labeling of a Lysine Residue in Human Serum Albumin

et al. 2014

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Conjugation to human serum albumin (HSA) has emerged as a powerful approach for extending the in vivo halflife of many small molecule and peptide/protein drugs. Current HSA conjugation strategies, however, can often yield heterogeneous mixtures with inadequate pharmacokinetics, low efficacies, and variable safety profiles. Here, we designed and synthesized analogues of TAK-242, a small molecule inhibitor of Toll-like receptor 4, that primarily reacted with a single lysine residue of HSA. These TAK-242-based cyclohexene compounds demonstrated robust reactivity, and Lys64 was identified as the primary conjugation site. A bivalent HSA conjugate was also prepared in a site-specific manner. Additionally, HSA-cyclohexene conjugates maintained higher levels of stability both in human plasma and in mice than the corresponding maleimide conjugates. This new conjugation strategy promises to broadly enhance the performance of HSA conjugates for numerous applications.

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Investigation of Non-Enzymatic Glycosylation of Human Serum Albumin Using Ion Trap-Time of Flight Mass Spectrometry

Cited by 31 publications

References 29 publications

Glycation of human serum albumin impairs binding to the glucagon-like peptide-1 analogue liraglutide

Glycation of human serum albumin impairs binding to the glucagon-like peptide-1 analogue liraglutide

Vitamin D prevents glycation of proteins: an in vitro study

Site‐Selective Labeling of a Lysine Residue in Human Serum Albumin

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