Treasure hunt for peptides with undefined chemical modifications: Proteomics identification of differential albumin adducts of 2-nitroimidazole-indocyanine green in hypoxic tumor.

Publisher: Wiley Country of Publication: England NLM ID: 9504818 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1096-9888 (Electronic) Linking ISSN: 10765174 NLM ISO Abbreviation: J Mass Spectrom Subsets: MEDLINE

Original Publication: Chichester, UK : Wiley, c1995-

Albumins*/analysis ; Albumins*/chemistry ; Peptides*/analysis ; Peptides*/chemistry ; Tumor Hypoxia*; Indocyanine Green/*chemistry ; Nitroimidazoles/*chemistry; Animals ; Mice ; Neoplasms, Experimental/diagnostic imaging ; Neoplasms, Experimental/metabolism ; Optical Imaging ; Proteome/analysis ; Proteome/chemistry ; Proteome/metabolism ; Proteomics/methods

2-Nitroimidazole is a well-known chemical probe targeting hypoxic environments of solid tumors, and its derivatives are widely used as imaging agents to investigate tissue and tumor hypoxia. However, the underlying chemistry for the hypoxia-detection capability of 2-nitroimidazole is still unclear. In this study, we deployed a biotin conjugate of 2-nitroimidazole-indocyanine green (2-nitro-ICG) for the investigation of in vivo hypoxia-probing mechanism of 2-nitro-ICG compounds. By implementing mass spectrometry-based proteomics and exhaustive data mining, we report that 2-nitro-ICG and its fragments modify mouse serum albumin as the primary protein target but at two structurally distinct sites and possibly via two different mechanisms. The identification of probe-modified peptides not only contributes to the understanding of the in vivo metabolism of 2-nitroimidazole compounds but also demonstrates a competent analytical workflow that enables the search for peptides with undefined modifications in complex proteome digests.
(© 2019 John Wiley & Sons, Ltd.)

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Keywords: 2-nitroimidazole; albumin adducts; chemical probe; hypoxia; proteomics

0 (Albumins)
0 (Nitroimidazoles)
0 (Peptides)
0 (Proteome)
IX6J1063HV (Indocyanine Green)

Date Created: 20190526 Date Completed: 20201208 Latest Revision: 20201214

20231215

10.1002/jms.4376

31128078