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De novo sequencing of heparan sulfate oligosaccharides by electron-activated dissociation

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De novo sequencing of heparan sulfate oligosaccharides by electron-activated dissociation. / Huang, Yu; Yu, Xiang; Mao, Yang; Costello, Catherine E; Zaia, Joseph; Lin, Cheng.

I: Analytical Chemistry, Bind 85, Nr. 24, 17.12.2013, s. 11979-86.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

Harvard

Huang, Y, Yu, X, Mao, Y, Costello, CE, Zaia, J & Lin, C 2013, 'De novo sequencing of heparan sulfate oligosaccharides by electron-activated dissociation', Analytical Chemistry, bind 85, nr. 24, s. 11979-86. https://doi.org/10.1021/ac402931j

APA

Huang, Y., Yu, X., Mao, Y., Costello, C. E., Zaia, J., & Lin, C. (2013). De novo sequencing of heparan sulfate oligosaccharides by electron-activated dissociation. Analytical Chemistry, 85(24), 11979-86. https://doi.org/10.1021/ac402931j

Vancouver

Huang Y, Yu X, Mao Y, Costello CE, Zaia J, Lin C. De novo sequencing of heparan sulfate oligosaccharides by electron-activated dissociation. Analytical Chemistry. 2013 dec 17;85(24):11979-86. https://doi.org/10.1021/ac402931j

Author

Huang, Yu ; Yu, Xiang ; Mao, Yang ; Costello, Catherine E ; Zaia, Joseph ; Lin, Cheng. / De novo sequencing of heparan sulfate oligosaccharides by electron-activated dissociation. I: Analytical Chemistry. 2013 ; Bind 85, Nr. 24. s. 11979-86.

Bibtex

@article{3d75b10a53ad4ec9abe4afb97504eec5,
title = "De novo sequencing of heparan sulfate oligosaccharides by electron-activated dissociation",
abstract = "Structural characterization of highly sulfated glycosaminoglycans (GAGs) by collisionally activated dissociation (CAD) is challenging because of the extensive sulfate losses mediated by free protons. While removal of the free protons may be achieved through the use of derivatization, metal cation adducts, and/or electrospray supercharging reagents, these steps add complexity to the experimental workflow. It is therefore desirable to develop an analytical approach for GAG sequencing that does not require derivatization or addition of reagents to the electrospray solution. Electron detachment dissociation (EDD) can produce extensive and informative fragmentation for GAGs without the need to remove free protons from the precursor ions. However, EDD is an inefficient process, often requiring consumption of large sample quantities (typically several micrograms), particularly for highly sulfated GAG ions. Here, we report that with improved instrumentation, optimization of the ionization and ion transfer parameters, and enhanced EDD efficiency, it is possible to generate highly informative EDD spectra of highly sulfated GAGs on the liquid chromatography (LC) timescale, with consumption of only a few nanograms of sample. We further show that negative electron transfer dissociation (NETD) is an even more effective fragmentation technique for GAG sequencing, producing fewer sulfate losses while consuming smaller amount of samples. Finally, a simple algorithm was developed for de novo HS sequencing based on their high-resolution tandem mass spectra. These results demonstrate the potential of EDD and NETD as sensitive analytical tools for detailed, high-throughput, de novo structural analyses of highly sulfated GAGs.",
keywords = "Carbohydrate Sequence, Electrons, Heparitin Sulfate, Informatics, Mass Spectrometry, Molecular Sequence Data, Oligosaccharides",
author = "Yu Huang and Xiang Yu and Yang Mao and Costello, {Catherine E} and Joseph Zaia and Cheng Lin",
year = "2013",
month = "12",
day = "17",
doi = "10.1021/ac402931j",
language = "English",
volume = "85",
pages = "11979--86",
journal = "Analytical Chemistry",
issn = "0003-2700",
publisher = "American Chemical Society",
number = "24",

}

RIS

TY - JOUR

T1 - De novo sequencing of heparan sulfate oligosaccharides by electron-activated dissociation

AU - Huang, Yu

AU - Yu, Xiang

AU - Mao, Yang

AU - Costello, Catherine E

AU - Zaia, Joseph

AU - Lin, Cheng

PY - 2013/12/17

Y1 - 2013/12/17

N2 - Structural characterization of highly sulfated glycosaminoglycans (GAGs) by collisionally activated dissociation (CAD) is challenging because of the extensive sulfate losses mediated by free protons. While removal of the free protons may be achieved through the use of derivatization, metal cation adducts, and/or electrospray supercharging reagents, these steps add complexity to the experimental workflow. It is therefore desirable to develop an analytical approach for GAG sequencing that does not require derivatization or addition of reagents to the electrospray solution. Electron detachment dissociation (EDD) can produce extensive and informative fragmentation for GAGs without the need to remove free protons from the precursor ions. However, EDD is an inefficient process, often requiring consumption of large sample quantities (typically several micrograms), particularly for highly sulfated GAG ions. Here, we report that with improved instrumentation, optimization of the ionization and ion transfer parameters, and enhanced EDD efficiency, it is possible to generate highly informative EDD spectra of highly sulfated GAGs on the liquid chromatography (LC) timescale, with consumption of only a few nanograms of sample. We further show that negative electron transfer dissociation (NETD) is an even more effective fragmentation technique for GAG sequencing, producing fewer sulfate losses while consuming smaller amount of samples. Finally, a simple algorithm was developed for de novo HS sequencing based on their high-resolution tandem mass spectra. These results demonstrate the potential of EDD and NETD as sensitive analytical tools for detailed, high-throughput, de novo structural analyses of highly sulfated GAGs.

AB - Structural characterization of highly sulfated glycosaminoglycans (GAGs) by collisionally activated dissociation (CAD) is challenging because of the extensive sulfate losses mediated by free protons. While removal of the free protons may be achieved through the use of derivatization, metal cation adducts, and/or electrospray supercharging reagents, these steps add complexity to the experimental workflow. It is therefore desirable to develop an analytical approach for GAG sequencing that does not require derivatization or addition of reagents to the electrospray solution. Electron detachment dissociation (EDD) can produce extensive and informative fragmentation for GAGs without the need to remove free protons from the precursor ions. However, EDD is an inefficient process, often requiring consumption of large sample quantities (typically several micrograms), particularly for highly sulfated GAG ions. Here, we report that with improved instrumentation, optimization of the ionization and ion transfer parameters, and enhanced EDD efficiency, it is possible to generate highly informative EDD spectra of highly sulfated GAGs on the liquid chromatography (LC) timescale, with consumption of only a few nanograms of sample. We further show that negative electron transfer dissociation (NETD) is an even more effective fragmentation technique for GAG sequencing, producing fewer sulfate losses while consuming smaller amount of samples. Finally, a simple algorithm was developed for de novo HS sequencing based on their high-resolution tandem mass spectra. These results demonstrate the potential of EDD and NETD as sensitive analytical tools for detailed, high-throughput, de novo structural analyses of highly sulfated GAGs.

KW - Carbohydrate Sequence

KW - Electrons

KW - Heparitin Sulfate

KW - Informatics

KW - Mass Spectrometry

KW - Molecular Sequence Data

KW - Oligosaccharides

U2 - 10.1021/ac402931j

DO - 10.1021/ac402931j

M3 - Journal article

C2 - 24224699

VL - 85

SP - 11979

EP - 11986

JO - Analytical Chemistry

JF - Analytical Chemistry

SN - 0003-2700

IS - 24

ER -

ID: 161581258