Proteins from Avastin® (bevacizumab) show tyrosine nitrations for which the consequences are completely unclear.

Avastin® (bevacizumab) is a protein drug widely used for cancer treatment although its further use is questionable due to serious side effects reported. As no systematic proteomic study on posttranslational modifications (PTMs) was reported so far, it was the aim of the current study to use a gel-ba...

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Autores principales:	Jia Wan, Edina Csaszar, Wei-Qiang Chen, Kongzhao Li, Gert Lubec
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/9856473a8af342a69c4c0b6cc2f6c8f6
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spelling	oai:doaj.org-article:9856473a8af342a69c4c0b6cc2f6c8f62021-11-18T07:22:06ZProteins from Avastin® (bevacizumab) show tyrosine nitrations for which the consequences are completely unclear.1932-620310.1371/journal.pone.0034511https://doaj.org/article/9856473a8af342a69c4c0b6cc2f6c8f62012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22523550/?tool=EBIhttps://doaj.org/toc/1932-6203Avastin® (bevacizumab) is a protein drug widely used for cancer treatment although its further use is questionable due to serious side effects reported. As no systematic proteomic study on posttranslational modifications (PTMs) was reported so far, it was the aim of the current study to use a gel-based proteomics method for determination of Avastin®-protein(s). Avastin® was run on two-dimensional gel electrophoresis (2-DE), spots were picked, followed by multi-enzyme in-gel digestion. Subsequently, the resulting peptides and posttranslational modifications were identified by mass spectrometry (nano-LC-ESI-MS/MS; HCT and LTQ Orbitrap MS). Heavy and light chains were observed and the 9 spots that were picked from 2DE-gels were identified as bevacizumab with high sequence coverage. MS/MS results showed multiple tyrosine nitrations on the Avastin® light and heavy chains that were either represented as nitrotyrosine or as aminotyrosine, which was shown to be generated from nitrotyrosine under reducing conditions. Protein nitration is known to significantly change protein functions and interactions and it may well be that some of the adverse effects of the protein drug Avastin® may be due to this PTM, which may have been generated during production--thus, nitration of Avastin® is a challenge for the pharmaceutical industry.Jia WanEdina CsaszarWei-Qiang ChenKongzhao LiGert LubecPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 4, p e34511 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jia Wan Edina Csaszar Wei-Qiang Chen Kongzhao Li Gert Lubec Proteins from Avastin® (bevacizumab) show tyrosine nitrations for which the consequences are completely unclear.
description	Avastin® (bevacizumab) is a protein drug widely used for cancer treatment although its further use is questionable due to serious side effects reported. As no systematic proteomic study on posttranslational modifications (PTMs) was reported so far, it was the aim of the current study to use a gel-based proteomics method for determination of Avastin®-protein(s). Avastin® was run on two-dimensional gel electrophoresis (2-DE), spots were picked, followed by multi-enzyme in-gel digestion. Subsequently, the resulting peptides and posttranslational modifications were identified by mass spectrometry (nano-LC-ESI-MS/MS; HCT and LTQ Orbitrap MS). Heavy and light chains were observed and the 9 spots that were picked from 2DE-gels were identified as bevacizumab with high sequence coverage. MS/MS results showed multiple tyrosine nitrations on the Avastin® light and heavy chains that were either represented as nitrotyrosine or as aminotyrosine, which was shown to be generated from nitrotyrosine under reducing conditions. Protein nitration is known to significantly change protein functions and interactions and it may well be that some of the adverse effects of the protein drug Avastin® may be due to this PTM, which may have been generated during production--thus, nitration of Avastin® is a challenge for the pharmaceutical industry.
format	article
author	Jia Wan Edina Csaszar Wei-Qiang Chen Kongzhao Li Gert Lubec
author_facet	Jia Wan Edina Csaszar Wei-Qiang Chen Kongzhao Li Gert Lubec
author_sort	Jia Wan
title	Proteins from Avastin® (bevacizumab) show tyrosine nitrations for which the consequences are completely unclear.
title_short	Proteins from Avastin® (bevacizumab) show tyrosine nitrations for which the consequences are completely unclear.
title_full	Proteins from Avastin® (bevacizumab) show tyrosine nitrations for which the consequences are completely unclear.
title_fullStr	Proteins from Avastin® (bevacizumab) show tyrosine nitrations for which the consequences are completely unclear.
title_full_unstemmed	Proteins from Avastin® (bevacizumab) show tyrosine nitrations for which the consequences are completely unclear.
title_sort	proteins from avastin® (bevacizumab) show tyrosine nitrations for which the consequences are completely unclear.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/9856473a8af342a69c4c0b6cc2f6c8f6
work_keys_str_mv	AT jiawan proteinsfromavastinbevacizumabshowtyrosinenitrationsforwhichtheconsequencesarecompletelyunclear AT edinacsaszar proteinsfromavastinbevacizumabshowtyrosinenitrationsforwhichtheconsequencesarecompletelyunclear AT weiqiangchen proteinsfromavastinbevacizumabshowtyrosinenitrationsforwhichtheconsequencesarecompletelyunclear AT kongzhaoli proteinsfromavastinbevacizumabshowtyrosinenitrationsforwhichtheconsequencesarecompletelyunclear AT gertlubec proteinsfromavastinbevacizumabshowtyrosinenitrationsforwhichtheconsequencesarecompletelyunclear
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Proteins from Avastin® (bevacizumab) show tyrosine nitrations for which the consequences are completely unclear.

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