Four unreported types of glycans containing mannose-6-phosphate are heterogeneously attached at three sites (including newly found Asn 233) to recombinant human acid alpha-glucosidase that is the only approved treatment for Pompe disease
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Park, Heajin | - |
dc.contributor.author | Kim, Jihye | - |
dc.contributor.author | Lee, Young Kwang | - |
dc.contributor.author | Kim, Wooseok | - |
dc.contributor.author | You, Seung Kwan | - |
dc.contributor.author | Do, Jonghye | - |
dc.contributor.author | Jang, Yeonjoo | - |
dc.contributor.author | Oh, Doo-Byung | - |
dc.contributor.author | Kim, Jae Il | - |
dc.contributor.author | Kim, Ha Hyung | - |
dc.date.available | 2019-01-22T14:13:42Z | - |
dc.date.issued | 2018-01-22 | - |
dc.identifier.issn | 0006-291X | - |
dc.identifier.issn | 1090-2104 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/cau/handle/2019.sw.cau/1308 | - |
dc.description.abstract | Myozyme is a recombinant human acid alpha-glucosidase (rhGAA) that is currently the only drug approved for treating Pompe disease, and its low efficacy means that a high dose is required. Mannose-6-phosphate (M6P) glycosylation on rhGAA is a key factor influencing lysosomal enzyme targeting and the efficacy of enzyme replacement therapy (ERT); however, its complex structure and relatively small quantity still remain to be characterized. This study investigated M6P glycosylation on rhGAA using liquid chromatography (LC) electrospray ionization (ESI)-high-energy collisional dissociation (HCD) tandem mass spectrometry (MS/MS). The glycans released from rhGAA were labeled with procainamide to improve mass ionization efficiency and the sensitivity of MS/MS. The relative quantities (%) of 78 glycans were obtained, and 1.0% of them were glycans containing M6P (M6P glycans). These were categorized according to their structure into 4 types: 3 newly found ones, comprising high-mannose-type M6P glycans capped with N-acetylglucosamine (GlcNAc) (2 variants, 17.5%), hybrid-type M6P glycans (2 variants, 11.2%), and hybrid-type M6P glycans capped with GlcNAc (3 variants, 6.9%), as well as high-mannose-type M6P glycans (3 variants, 64.4%). HCD-MS/MS spectra identified six distinctive M6P-derived oxonium ions. The glycopeptides obtained from protease-digested rhGAA were analyzed using nano-LC-ESI-HCD-MS/MS, and the extracted-ion chromatograms of M6P-derived oxonium ions confirmed three M6P glycosylation sites comprising Asn 140, Asn 233 (newly found), and Asn 470 attached heterogeneously to nine M6P glycans (two types), eight M6P glycans (four types), and seven M6P glycans (two types), respectively. This is the first study of rhGAA to differentiate M6P glycans and identify their attachment sites, despite rhGAA already being an approved drug for Pompe disease. (C) 2017 Elsevier Inc. All rights reserved. | - |
dc.format.extent | 7 | - |
dc.publisher | ACADEMIC PRESS INC ELSEVIER SCIENCE | - |
dc.title | Four unreported types of glycans containing mannose-6-phosphate are heterogeneously attached at three sites (including newly found Asn 233) to recombinant human acid alpha-glucosidase that is the only approved treatment for Pompe disease | - |
dc.type | Article | - |
dc.identifier.doi | 10.1016/j.bbrc.2017.12.101 | - |
dc.identifier.bibliographicCitation | BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, v.495, no.4, pp 2418 - 2424 | - |
dc.description.isOpenAccess | N | - |
dc.identifier.wosid | 000426336300006 | - |
dc.identifier.scopusid | 2-s2.0-85039158850 | - |
dc.citation.endPage | 2424 | - |
dc.citation.number | 4 | - |
dc.citation.startPage | 2418 | - |
dc.citation.title | BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | - |
dc.citation.volume | 495 | - |
dc.type.docType | Article | - |
dc.publisher.location | 미국 | - |
dc.subject.keywordAuthor | Acid alpha-glucosidase | - |
dc.subject.keywordAuthor | Glycan | - |
dc.subject.keywordAuthor | Mannose-6-phosphate | - |
dc.subject.keywordAuthor | High-energy collisional dissociation | - |
dc.subject.keywordAuthor | M6P glycosylation site | - |
dc.subject.keywordPlus | HYDROPHILIC INTERACTION CHROMATOGRAPHY | - |
dc.subject.keywordPlus | LYSOSOMAL STORAGE DISORDERS | - |
dc.subject.keywordPlus | MASS-SPECTROMETRY | - |
dc.subject.keywordPlus | PROTEIN GLYCOSYLATION | - |
dc.subject.keywordPlus | THERAPEUTIC ENZYMES | - |
dc.subject.keywordPlus | N-GLYCANS | - |
dc.subject.keywordPlus | IDENTIFICATION | - |
dc.subject.keywordPlus | PROCAINAMIDE | - |
dc.subject.keywordPlus | EFFICACY | - |
dc.subject.keywordPlus | MILK | - |
dc.relation.journalResearchArea | Biochemistry & Molecular Biology | - |
dc.relation.journalResearchArea | Biophysics | - |
dc.relation.journalWebOfScienceCategory | Biochemistry & Molecular Biology | - |
dc.relation.journalWebOfScienceCategory | Biophysics | - |
dc.description.journalRegisteredClass | sci | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.
84, Heukseok-ro, Dongjak-gu, Seoul, Republic of Korea (06974)02-820-6194
COPYRIGHT 2019 Chung-Ang University All Rights Reserved.
Certain data included herein are derived from the © Web of Science of Clarivate Analytics. All rights reserved.
You may not copy or re-distribute this material in whole or in part without the prior written consent of Clarivate Analytics.