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Treasure hunt for peptides with undefined chemical modifications: Proteomics identification of differential albumin adducts of 2‐nitroimidazole‐indocyanine green in hypoxic tumor
Author(s) -
Wang Lei,
Dietz Christopher,
Zhou Feifei,
Erfanzadeh Mohsen,
Zhu Quing,
Smith Michael B.,
Yao Xudong
Publication year - 2020
Publication title -
journal of mass spectrometry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.475
H-Index - 121
eISSN - 1096-9888
pISSN - 1076-5174
DOI - 10.1002/jms.4376
Subject(s) - nitroimidazole , chemistry , indocyanine green , in vivo , proteome , proteomics , albumin , mass spectrometry , conjugate , biochemistry , combinatorial chemistry , chromatography , pathology , organic chemistry , medicine , mathematical analysis , microbiology and biotechnology , mathematics , gene , biology
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.