What does this strategy enable?
The modular reactivity-encoding platform (MREP) uses distinct alkyne-tagged probes for carboxyl, amine, carbonyl and thiol functionalities. Tagged metabolites are captured through click chemistry on a common resin, matrix is removed, and released derivatives share reporter-ion behavior. The strategy converts intrinsic chemical reactivity into an experimental annotation/enrichment dimension.
Transferable workflow
Workflow
- 1
Select a functional-group-specific probe
Choose a chemoselective probe for the metabolite reactivity class of interest, such as carboxyl, amine, carbonyl or thiol groups.
- 2
Encode metabolites by covalent derivatization
React the sample under conditions designed to selectively label the targeted functional group.
- 3
Capture and clean up the encoded submetabolome
Use click chemistry and solid-phase capture to enrich tagged metabolites while reducing matrix background.
- 4
Release and analyze derivatives by LC-MS/MS
Profile enriched derivatives, using shared reporter behavior and functional-group information to aid classification and annotation.
- 5
Reconstruct reactivity-resolved metabolome layers
Compare the parallel functional-group-defined measurements to expand detectable chemical space and interpret metabolic changes.
Strategy profile
Related objectives
Metabolite annotation, Molecular discovery
Components
Sample preparation, Chromatography, Data acquisition, Annotation or identification, Biological validation
Sample types
Serum, Tissue or biopsy
Biological context
Animal
Organisms
Mus musculus
Scope and considerations
Designed for
- Expanding metabolite coverage through functional-group-selective enrichment and reporter chemistry.
- Separating complex metabolomes into chemically interpretable reactivity classes.
Important requirements
- Validated chemoselective reagents and controls for reaction selectivity.
- Careful assessment of derivatization yield, matrix effects and quantitative behavior.
Considerations
- Probe selectivity and conversion efficiency are chemistry-dependent.
- Derivatization changes retention, ionization and fragmentation and therefore requires method-specific references.
- The source demonstrates mouse serum and liver; transfer to other organisms and matrices requires method validation.
Reusable resources
Publication
Tao X, Zhang C-M, Yang R-J, et al. Chemoselective Metabolomics via a Modular Reactivity-Encoding Platform. Advanced Science (2026).