Abstract
The catechol quinone (CQ) motif is present in many biologically relevant molecules throughout endogenous metabolic products, foods, drugs, and environmental pollutants. The CQ derivatives may undergo Michael addition, and has been shown to yield covalent bonds with nucleophilic sites of cysteine, lysine, or histidine residue of proteins. The CQ-adducted proteins may exhibit cytotoxicity or biological functions different from their un-adducted forms. Identification, characterization, and quantification of relevant protein targets are essential but challenging goals. Mass spectrometry (MS) is well-suited for the analysis of proteins and protein modifications. Technical development of bottom-up proteomics has greatly advanced the field of biomolecular MS, including protein adductomics. This mini-review focuses on the use of biomolecular MS in (1) structural and functional characterization of CQ adduction on standards of proteins, (2) identification of endogenous adduction targets, and (3) quantification of adducted blood proteins as exposure index. The reactivity and outcome of CQ adduction are discussed with emphases on endogenous species, such as dopamine and catechol estrogens. Limitations and advancements in sample preparation, MS instrumentation, and software to facilitate protein adductomics are also discussed.
Highlights
Catechol-type polyphenols derived from endogenous metabolism or food/drugs are transformed to o-quinones accompanied by induced cellular bioactivities
Functional changes induced by catechol quinone (CQ) adduction of these standards can be classified as (1) altered protein activity due to covalent conjugation with the free thiol, (2) altered protein stability due to modification of hydrophilic residues by lipophilic CQ derivatives, and (3) altered cell signaling due to hindered receptor or enzyme recognition domain
From an insulin resistance patient’s blood, endogenous adduction of human serum albumin (HSA) and IgG1 at multiple Cys or Lys sites was initially identified by database search and confirmed by retention time and spectra matching with adducted protein standards
Summary
Catechol-type polyphenols derived from endogenous metabolism or food/drugs are transformed to o-quinones accompanied by induced cellular bioactivities. Another major reaction that competes with redox cycling of CQs is the covalent conjugation of o-quinone with nucleophilic sites on proteins or DNAs (Figure 1). This review will focus on the biomolecular MS and proteomics approach for identification, characterization, and quantification of CQ-derived protein adducts.
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