Establishing Signature Fragments for Identification and Sequencing of Dityrosine Cross-Linked Peptides Using Ultraviolet Photodissociation Mass Spectrometry

S Mukherjee; M Fang; WM Kok; EA Kapp; VJ Thombare; R Huguet; CA Hutton; GE Reid; BR Roberts

Journal article

Establishing Signature Fragments for Identification and Sequencing of Dityrosine Cross-Linked Peptides Using Ultraviolet Photodissociation Mass Spectrometry

S Mukherjee, M Fang, WM Kok, EA Kapp, VJ Thombare, R Huguet, CA Hutton, GE Reid, BR Roberts

Analytical Chemistry | AMER CHEMICAL SOC | Published : 2019

DOI: 10.1021/acs.analchem.9b02986

Abstract

Dityrosine cross-linking of Aβ peptides and α-synuclein is increasingly becoming recognized as a biomarker of neuropathological diseases. However, there remains a need for the development of analytical methods that enable the specific and selective identification of dityrosine cross-linked proteins and peptides in complex biological samples. Here, we report that the gas-phase fragmentation of protonated dityrosine cross-linked peptides under ultraviolet photodissociation (UVPD) tandem mass spectrometry (MS/MS) conditions results in the cleavage across Cα and Cβ atoms of the dityrosine residue. This Cα-Cβ cleavage in UVPD-MS/MS results in the formation of diagnostic pairs of product ions, pro..

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University of Melbourne Researchers

Craig Hutton Author

Gavin Reid Author

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Grants

Awarded by Alzheimer's Drug Discovery Foundation

Funding Acknowledgements

The authors acknowledge funding from the Victorian Government's Operational Infrastructure Support program, the National Health and Medical Research Council Grants APP1138673 and APP1164692 (B.R.R.), Alzheimer's Disease Drug Discovery Foundation (ADDF) (B.R.R.), and the Australian Research Council Grants LE160100015 (G.E.R), DP190102464 (G.E.R.), DP120101454 (C.A.H.), and DP140100174 (C.A.H.).