Chemical modifications of lysyl and arginyl residues of human plasma α1-antitrypsin

1976 ◽  
Vol 177 (2) ◽  
pp. 552-560 ◽  
Author(s):  
Thomas F. Busby ◽  
Jose C. Gan
Keyword(s):  
Human Plasma ◽  
Chemical Modifications ◽  
Arginyl Residues

scholarly journals Global chemical modifications comparison of human plasma proteomes from two different age groups

2020 ◽  
Author(s):  
Yongtao Liu ◽  
Mindi Zhao ◽  
Xuanzhen Pan ◽  
Youhe Gao
Keyword(s):  
Amino Acid ◽  
Human Plasma ◽  
Age Groups ◽  
Young Group ◽  
Structure And Function ◽  
Plasma Proteome ◽  
Chemical Modifications ◽  
Old People ◽  
And Function ◽  
Human Plasma Proteome

AbstractThe chemical modification of proteins refers to the covalent group reaction involved in their amino acid residues or chain ends which, in turn, change the molecular structure and function of the proteins. There are many types of molecular modifications in the human plasma proteome, such as phosphorylation, methylation, and acetylation. In this study, two groups of human plasma proteome at different age groups (old and young) were used to perform a comparison of global chemical modifications, as determined by tandem mass spectrometry (MS/MS) combined with non-limiting modification identification algorithms. The sulfhydryl in the cysteine A total of 4 molecular modifications were found to have significant differences: the succinylation and phosphorylation modification of cysteine (Cys, C) and the modification of lysine (Lys, K) with threonine (Thr, T) were significantly higher in the old group than in the young group, while the carbamylation of lysine was lower in the young group. Cysteine residue is an important group for forming disulphide bonds and maintaining the structure of the protein. Differential cysteine-related sulfydryl modifications may cause structural and functional changes. Lysine is a basic amino acid, and the modification of its amino group will change the charge state of the protein, which may affect the structure and function of the protein. In summary, four types of protein chemical modifications and substitutes were found to be significantly different in the plasma proteome in different age groups and their probabilities of random generation are lower by passing random grouping test. We speculate that there is an increase in certain modified proteins in the blood of the old people which, in turn, changes the function of those proteins. This change may be one of the reasons why the old people are more likely than the young people to be at risk for age-related diseases, such as metabolic diseases, cerebral and cardiovascular diseases, and cancer.

scholarly journals Global chemical modifications comparison of human plasma proteome from two different age groups

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Yongtao Liu ◽  
Xuanzhen Pan ◽  
Mindi Zhao ◽  
Youhe Gao
Keyword(s):  
Human Plasma ◽  
Metabolic Diseases ◽  
Age Groups ◽  
Young Group ◽  
Tandem Mass ◽  
Plasma Proteome ◽  
Chemical Modifications ◽  
Old People ◽  
Age Related ◽  
Human Plasma Proteome

Abstract In this study, two groups of human plasma proteome at different age groups (old and young) were used to perform a comparison of global chemical modifications, as determined by tandem mass spectrometry (MS/MS) combined with non-limiting modification identification algorithms. The sulfhydryl in the cysteine A total of 4 molecular modifications were found to have significant differences passing random grouping tests: the succinylation and phosphorylation modification of cysteine (Cys, C) and the modification of lysine (Lys, K) with threonine (Thr, T) were significantly higher in the old group than in the young group, while the carbamylation of lysine was lower in the young group. We speculate that there is an increase in certain modified proteins in the blood of the old people which, in turn, changes the function of those proteins. This change may be one of the reasons why old people are more likely than young people to be at risk for age-related diseases, such as metabolic diseases, cerebral and cardiovascular diseases, and cancer.

High-sensitivity workflow for LC–MS-based analysis of GalNAc-conjugated oligonucleotides: a case study

Bioanalysis ◽  
2021 ◽  
Author(s):  
Aaron R Ledvina ◽  
Matthew Ewles ◽  
Paul Severin ◽  
David Good ◽  
Cecilia Arfvidsson
Keyword(s):  
Human Plasma ◽  
High Sensitivity ◽  
Pharmacokinetic Profile ◽  
Valuable Insight ◽  
Chemical Modifications ◽  
Mass Fragment ◽  
Specific Measurement ◽  
Low Mass

Aim: Mass-selective quantitation is a powerful attribute of LC–MS as a platform for bioanalysis. Here, a sensitive LC–MS approach has been validated for an oligonucleotide having chemical modifications (e.g., N-acetylgalactosamine [GalNAc] conjugated), to distinguish between the conjugated and unconjugated forms of the oligonucleotide, thereby enabling a nuanced view of the pharmacokinetic profile. Results: A high-sensitivity methodology for mass-specific measurement of AZD8233, a GalNAc-conjugated 16-mer oligonucleotide, using LLE-SPE with optimized LC conditions and detection of a low-mass fragment ion was successfully validated in the range of 0.20–100 ng/ml in human plasma. Conclusion: The AZD8233 LC–MS methodology adds valuable insight on the GalNAc linker’s in vivo stability to the program and should be broadly applicable to oligonucleotides requiring high sensitivity and mass-selective measurement for quantitative discrimination from metabolites and endogenous interferences.

Performances of an Artificial Reagent for the One-stage Factor IX Assay

1975 ◽  
Vol 33 (03) ◽  
pp. 547-552 ◽  
Author(s):  
L Meunier ◽  
J. P Allain ◽  
D Frommel
Keyword(s):  
Human Plasma ◽  
Factor Ix ◽  
Severe Haemophilia ◽  
Normal Human Plasma ◽  
Haemophilia B ◽  
One Stage ◽  
Normal Human ◽  
The One

SummaryA mixture of adsorbed normal human plasma and chicken plasma was prepared as reagent for factor IX measurement using a one-stage method. The substrate was found to be specific for factor IX. Its performances tested on samples displaying factor IX activity ranging from <l%–2,500% compared favorably with those obtained when using the plasma of severe haemophilia B patients as substrate.

Plasma Components which Interfere with Ristocetin-induced Platelet Aggregation

1975 ◽  
Vol 33 (03) ◽  
pp. 540-546 ◽  
Author(s):  
Robert F Baugh ◽  
James E Brown ◽  
Cecil Hougie
Keyword(s):  
Platelet Aggregation ◽  
Human Plasma ◽  
Plasma Proteins ◽  
Binding Protein ◽  
Plasma Heating ◽  
Protein S ◽  
Fold Increase ◽  
Normal Human Plasma ◽  
Preliminary Examination ◽  
Normal Human

SummaryNormal human plasma contains a component or components which interfere with ristocetin-induced platelet aggregation. Preliminary examination suggests a protein (or proteins) which binds ristocetin and competes more effectively for ristocetin than do the proteins involved in ristocetin-induced platelet aggregation. The presence of this protein in normal human plasma also prevents ristocetin-induced precipitation of plasma proteins at levels of ristocetin necessary to produce platelet aggregation (0.5–2.0 mg/ml). Serum contains an apparent two-fold increase of this component when compared with plasma. Heating serum at 56° for one hour results in an additional 2 to 4 fold increase. The presence of a ristocetin-binding protein in normal human plasma requires that this protein be saturated with ristocetin before ristocetin-induced platelet aggregation will occur. Variations in the ristocetin-binding protein(s) will cause apparent discrepancies in ristocetin-induced platelet aggregation in normal human plasmas.

Studies on the Fibrinolytic System in Human Plasma: Quantitative Determination of Plasminogen Activators and Proactivators

1979 ◽  
Vol 41 (02) ◽  
pp. 365-383 ◽  
Author(s):  
C Kluft
Keyword(s):  
Pilot Study ◽  
Plasma Level ◽  
Human Plasma ◽  
Plasminogen Activators ◽  
Venous Occlusion ◽  
Quantitative Information ◽  
Optimal Recovery ◽  
Dextran Sulphate ◽  
Baseline Levels

SummaryEffects due to plasma plasminogen activators and proactivators are usually studied in assay systems where inhibitors influence the activity and where the degree of activation of proactivators is unknown. Quantitative information on activator and proactivator levels in plasma is therefore not availableStudies on the precipitating and activating properties of dextran sulphate in euglobulin fractionation presented in this paper resulted in the preparation of a fraction in which there was optimal recovery and optimal activation of a number of plasminogen activators and proactivators from human plasma. The quantitative assay of these activators on plasminogen-rich fibrin plates required the addition of flufenamate to eliminate inhibitors. The response on the fibrin plates (lysed zones) could be coverted to arbitrary blood activator units (BAU). Consequently, a new activator assay which enables one to quantitatively determine the plasma level of plasminogen activators and proactivators together is introduced.Two different contributions could be distinguished: an activity originating from extrinsic activator and one originating from intrinsic proactivators. The former could be assayed separately by means of its resistance to inhibition by Cl-inactivator. Considering the relative concentrations of extrinsic and intrinsic activators, an impression of the pattern of activator content in plasma was gained. In morning plasma with baseline levels of fibrinolysis, the amount of extrinsic activator was negligible as compared to the level of potentially active intrinsic activators. Consequently, the new assay nearly exclusively determines the level of intrinsic activators in morning plasma. A pilot study gave a fairly stable level of 100 ± 15 BAU/ml (n = 50). When fibrinolysis was stimulated by venous occlusion (15 min), the amount of extrinsic activator was greatly increased, reaching a total activator level of 249 ± 27 BAU/ml (n = 7).

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