Complete mapping of disulfide linkages for etanercept products by multi-enzyme digestion coupled with LC-MS/MS using multi-fragmentations including CID and ETD

Li Juan Huang, Chia Wang Chiang, Shun Li Chen, Shih Yao Wei, Shu Hui Chen

研究成果: Article

摘要

The disulfide linkages of two etanercept products, Enbrel® (innovator drug) and TuNEX®, were characterized and compared using a multi-fragmentation approach consisting of electron transfer dissociation (ETD) and collision induced dissociation (CID) in combination with multi-enzyme digestion protocols (from Lys-C, trypsin, Glu-C, and PNGase F). Multi-fragmentation approach allowed multi-disulfide linkages contained in a peptide to be un-ambiguously assigned based on the cleavage of both the disulfide and the backbone linkages in a MS 3 schedule. New insights gained using this approach were discussed. A total of 29 disulfides, Cys18-Cys31, Cys32-Cys45, Cys35-Cys53, Cys56-Cys71, Cys74-Cys88, Cys78-Cys-96, Cys98-Cys104, Cys112-Cys121, Cys115-Cys139, Cys-142-Cys157, Cys163-Cys178 in TNFR portion and Cys240-Cys240, Cys246-Cys246, Cys249-Cys249, Cys281-Cys341, Cys387-Cys445 in IgG1 Fc domain, were completely assigned with the demonstration of the same disulfide linkages between the Enbrel® and TuNEX® products. The data showed the higher order structure was preserved throughout the recombinant manufacturing processes and consistent between the two products.

原文English
頁(從 - 到)531-541
頁數11
期刊Journal of Food and Drug Analysis
27
發行號2
DOIs
出版狀態Published - 2019 四月

指紋

Chromosome Mapping
sulfides
Disulfides
electron transfer
Digestion
digestion
Electrons
Enzymes
enzymes
Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase
Trypsin
trypsin
Appointments and Schedules
manufacturing
Immunoglobulin G
Etanercept
tandem mass spectrometry
peptides
drugs
Peptides

All Science Journal Classification (ASJC) codes

  • Food Science
  • Pharmacology

引用此文

@article{cff1c175edcf43429ca13694f77f4707,
title = "Complete mapping of disulfide linkages for etanercept products by multi-enzyme digestion coupled with LC-MS/MS using multi-fragmentations including CID and ETD",
abstract = "The disulfide linkages of two etanercept products, Enbrel{\circledR} (innovator drug) and TuNEX{\circledR}, were characterized and compared using a multi-fragmentation approach consisting of electron transfer dissociation (ETD) and collision induced dissociation (CID) in combination with multi-enzyme digestion protocols (from Lys-C, trypsin, Glu-C, and PNGase F). Multi-fragmentation approach allowed multi-disulfide linkages contained in a peptide to be un-ambiguously assigned based on the cleavage of both the disulfide and the backbone linkages in a MS 3 schedule. New insights gained using this approach were discussed. A total of 29 disulfides, Cys18-Cys31, Cys32-Cys45, Cys35-Cys53, Cys56-Cys71, Cys74-Cys88, Cys78-Cys-96, Cys98-Cys104, Cys112-Cys121, Cys115-Cys139, Cys-142-Cys157, Cys163-Cys178 in TNFR portion and Cys240-Cys240, Cys246-Cys246, Cys249-Cys249, Cys281-Cys341, Cys387-Cys445 in IgG1 Fc domain, were completely assigned with the demonstration of the same disulfide linkages between the Enbrel{\circledR} and TuNEX{\circledR} products. The data showed the higher order structure was preserved throughout the recombinant manufacturing processes and consistent between the two products.",
author = "Huang, {Li Juan} and Chiang, {Chia Wang} and Chen, {Shun Li} and Wei, {Shih Yao} and Chen, {Shu Hui}",
year = "2019",
month = "4",
doi = "10.1016/j.jfda.2018.11.007",
language = "English",
volume = "27",
pages = "531--541",
journal = "Journal of Food and Drug Analysis",
issn = "1021-9498",
publisher = "National Laboratories of Foods and Drugs",
number = "2",

}

TY - JOUR

T1 - Complete mapping of disulfide linkages for etanercept products by multi-enzyme digestion coupled with LC-MS/MS using multi-fragmentations including CID and ETD

AU - Huang, Li Juan

AU - Chiang, Chia Wang

AU - Chen, Shun Li

AU - Wei, Shih Yao

AU - Chen, Shu Hui

PY - 2019/4

Y1 - 2019/4

N2 - The disulfide linkages of two etanercept products, Enbrel® (innovator drug) and TuNEX®, were characterized and compared using a multi-fragmentation approach consisting of electron transfer dissociation (ETD) and collision induced dissociation (CID) in combination with multi-enzyme digestion protocols (from Lys-C, trypsin, Glu-C, and PNGase F). Multi-fragmentation approach allowed multi-disulfide linkages contained in a peptide to be un-ambiguously assigned based on the cleavage of both the disulfide and the backbone linkages in a MS 3 schedule. New insights gained using this approach were discussed. A total of 29 disulfides, Cys18-Cys31, Cys32-Cys45, Cys35-Cys53, Cys56-Cys71, Cys74-Cys88, Cys78-Cys-96, Cys98-Cys104, Cys112-Cys121, Cys115-Cys139, Cys-142-Cys157, Cys163-Cys178 in TNFR portion and Cys240-Cys240, Cys246-Cys246, Cys249-Cys249, Cys281-Cys341, Cys387-Cys445 in IgG1 Fc domain, were completely assigned with the demonstration of the same disulfide linkages between the Enbrel® and TuNEX® products. The data showed the higher order structure was preserved throughout the recombinant manufacturing processes and consistent between the two products.

AB - The disulfide linkages of two etanercept products, Enbrel® (innovator drug) and TuNEX®, were characterized and compared using a multi-fragmentation approach consisting of electron transfer dissociation (ETD) and collision induced dissociation (CID) in combination with multi-enzyme digestion protocols (from Lys-C, trypsin, Glu-C, and PNGase F). Multi-fragmentation approach allowed multi-disulfide linkages contained in a peptide to be un-ambiguously assigned based on the cleavage of both the disulfide and the backbone linkages in a MS 3 schedule. New insights gained using this approach were discussed. A total of 29 disulfides, Cys18-Cys31, Cys32-Cys45, Cys35-Cys53, Cys56-Cys71, Cys74-Cys88, Cys78-Cys-96, Cys98-Cys104, Cys112-Cys121, Cys115-Cys139, Cys-142-Cys157, Cys163-Cys178 in TNFR portion and Cys240-Cys240, Cys246-Cys246, Cys249-Cys249, Cys281-Cys341, Cys387-Cys445 in IgG1 Fc domain, were completely assigned with the demonstration of the same disulfide linkages between the Enbrel® and TuNEX® products. The data showed the higher order structure was preserved throughout the recombinant manufacturing processes and consistent between the two products.

UR - http://www.scopus.com/inward/record.url?scp=85059567285&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85059567285&partnerID=8YFLogxK

U2 - 10.1016/j.jfda.2018.11.007

DO - 10.1016/j.jfda.2018.11.007

M3 - Article

C2 - 30987725

AN - SCOPUS:85059567285

VL - 27

SP - 531

EP - 541

JO - Journal of Food and Drug Analysis

JF - Journal of Food and Drug Analysis

SN - 1021-9498

IS - 2

ER -