Post‐Translational Modifications in the Context of Therapeutic Proteins: An Introductory Overview

Walsh, Gary

doi:10.1002/9783527626601.ch1

Cited by 10 publications

(10 citation statements)

References 18 publications

(16 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Glycosylation patterns largely influence immunogenicity and half-life 48. More complex glycosylation patterns have a higher number of sialic acid residues with longer half-lives 68,74. Sialic acid carbohydrate content affects serum half-life, with increased sialic acid content resulting in longer half-life.…”

Section: Pharmacologymentioning

confidence: 99%

Epoetin zeta in the management of anemia associated with chronic kidney disease, differential pharmacology and clinical utility

Davis–Ajami¹,

Wu²,

Downton³

et al. 2014

BTT

View full text Add to dashboard Cite

Epoetin zeta was granted marketing authorization in October 2007 by the European Medicines Agency as a recombinant human erythropoietin erythropoiesis-stimulating agent to treat symptomatic anemia of renal origin in adult and pediatric patients on hemodialysis and adults on peritoneal dialysis, as well as for symptomatic renal anemia in adult patients with renal insufficiency not yet on dialysis. Currently, epoetin zeta can be administered either subcutaneously or intravenously to correct for hemoglobin concentrations ≤10 g/dL (6.2 mmol/L) or with dose adjustment to maintain hemoglobin levels at desired levels not in excess of 12 g/dL (7.5 mmol/L). This review article focuses on epoetin zeta indications in chronic kidney disease, its use in managing anemia of renal origin, and discusses its pharmacology and clinical utility.

show abstract

Section: Pharmacologymentioning

confidence: 99%

Epoetin zeta in the management of anemia associated with chronic kidney disease, differential pharmacology and clinical utility

Davis–Ajami¹,

Wu²,

Downton³

et al. 2014

BTT

View full text Add to dashboard Cite

show abstract

“…Various protein post-translational modifications (PTM's) have been well documented as major contributors to heterogeneity in recombinant monoclonal antibodies 1-5 . Some of these processes occur during fermentation, such as glycosylation and sialic acid incorporation; 6-8 while others can occur through purification, storage and even sample preparation, such as oxidation and disulfide bond scrambling 9-10 .…”

mentioning

confidence: 99%

Arginine Modifications by Methylglyoxal: Discovery in a Recombinant Monoclonal Antibody and Contribution to Acidic Species

Chumsae

Gifford²,

Lian³

et al. 2013

Anal. Chem.

View full text Add to dashboard Cite

Heterogeneity is common among protein therapeutics. For example, the so-called acidic species (charge variants) are typically observed when recombinant monoclonal antibodies (mAbs) are analyzed by weak-cation exchange chromatography (WCX). Several protein post-translational modifications have been established as contributors, but still cannot completely account for all heterogeneity. As reported herein, an unexpected modification by methylglyoxal (MGO) was identified, for the first time, in a recombinant monoclonal antibody expressed in Chinese hamster ovary (CHO) cells. Modifications of arginine residues by methylglyoxal lead to two adducts (dihydroxyimidazolidine and hydroimidazolone) with increase of molecular weights of 72 and 54 Daltons, respectively. In addition, the modification by methylglyoxal causes the antibody to elute earlier in the weak cation exchange chromatogram. Consequently, the extent to which an antibody was modified at multiple sites corresponds to the degree of shift in elution time. Furthermore, cell culture parameters also affected the extent of modifications by methylglyoxal, a highly reactive metabolite that can be generated from glucose or lipids or other metabolic pathways. Our findings again highlight the impact that cell culture conditions can have on the product quality of recombinant protein pharmaceuticals.

show abstract

“…It is possible to find posttranslational modifications in animal proteins due to the action of different physical, enzymatic, and chemical treatments (acetylation, deamination, nitration, methylation, lipidation, carboxylation, formation of disulfide bonds, hydroxylation, sulfation, amidation, and glycosylation) [10][11][12]. A wide variety of posttranslational modifications have been characterized; some of them are formed mostly in intracellular proteins such as the phosphorylation mechanism, and conversely there are some other processes such as glycosylation, nonenzymatic glycation, formation of disulfide bonds, and carboxylation, which are formed in extracellular proteins [13].…”

Section: Posttranslational Modifications Of Proteinsmentioning

confidence: 99%

Glycation of Animal Proteins Via Maillard Reaction and Their Bioactivity

Mondaca-Navarro¹,

Ramírez²,

Lerma³

et al. 2020

Food Processing

View full text Add to dashboard Cite

Nowadays there has been an increase in the need to incorporate foods in our diets that have optimal and palatable organoleptic characteristics as well as complex interaction in human biological processes that provide beneficial properties to human health. Animal foods and their by-products are an important source of macro-and micronutrients and also a great protein source; nevertheless the consumption of these products has been decreasing since they have been associated with the generation of chronic degenerative diseases; therefore the food industry has sought to innovate toward the generation of healthier foods. This chapter presents an overview of the glycation of proteins of animal origin via the Maillard reaction emphasizing on their posttranslational modifications and their possible uses in food, based on their bioactivity.

show abstract

Post‐Translational Modifications in the Context of Therapeutic Proteins: An Introductory Overview

Cited by 10 publications

References 18 publications

Epoetin zeta in the management of anemia associated with chronic kidney disease, differential pharmacology and clinical utility

Epoetin zeta in the management of anemia associated with chronic kidney disease, differential pharmacology and clinical utility

Arginine Modifications by Methylglyoxal: Discovery in a Recombinant Monoclonal Antibody and Contribution to Acidic Species

Glycation of Animal Proteins Via Maillard Reaction and Their Bioactivity

Contact Info

Product

Resources

About