Chemoproteomics bridges chemical biology and proteomics, delivering mechanistic, proteome-wide insights that accelerate hit-to-lead/lead optimization stages in small molecule drug discovery. Bionosys’ LiP-MS technology provides a unique label-free approach that can identify binding targets in complex proteomes.
The principle behind LiP-MS is simple: When a small molecule binds to a protein, it alters three-dimensional conformation of the protein, which changes the regions that are exposed and accessible to proteolytic cleavage. These structural shifts produce distinctive peptide fingerprints that are captured, quantified, and compared between compound-treated and untreated samples.
TrueTarget is Biognosys’s fully industrialized LiP-MS platform, purpose-built for unbiased target deconvolution, mechanism-of-action elucidation, and selectivity profiling.
LiP-MS is applicable across diverse biological matrices and is designed to support both target-based and phenotypic drug discovery programs. Whether you are identifying the primary target of a phenotypic hit, profiling off-target liabilities, or elucidating a compound’s mechanism of action, LiP-MS delivers the proteome-wide context needed to make confident, data-driven decisions.
Target identification in complex
proteomes.
Mapping of binding sites in native cellular context.
No compound modification, cell line engineering or affinity enrichment required.
Unbiased global target ID ensures both primary targets and off-target effects are captured simultaneously.
Probe compound-protein interactions for over 250,000 peptides, covering up to 9,000 proteins across the proteome.
1. Native Cell Lysis
Cells are lysed under non-denaturing, native conditions to keep proteins in their physiologically relevant folding states.
2. Compound Incubation
The compound is added for a short incubation period allowing it to bind its targets directly within the native proteome, with no requirement for labeling or chemical modification of the compound.
3. Limited Proteolysis (LiP)
Proteins undergo a brief proteolysis under native conditions using a non-specific protease which cleaves in a structure-specific manner, i.e. compound-bound or conformationally altered sites produce a distinct cleavage pattern.
4. Complete Tryptic Digestion
A second, complete digestion with trypsin under denaturing conditions generates peptides suitable to bottom-up mass spectrometry analysis.
5. DIA Mass Spectrometry & ML Scoring
Peptides are quantified across a seven-concentration dose-response experiment and processed through a machine-learning framework that calculates a LiP-score to rank potential targets and predict possible binding sites.
Proteomics Service
LiP‑MS enables proteome‑wide detection of compound‑induced structural changes at peptide‑level resolution. In a single, label‑free experiment, the approach quantifies over 250,000 peptides across up to 9,000 proteins, revealing direct targets, off‑target interactions, allosteric effects, and potential toxicity liabilities. The resulting structural fingerprints allow confident comparison between treated and untreated samples.
LiP‑MS supports target identification and prioritization across early drug discovery programs. Applications include proteome‑wide target ranking, prediction of compound binding sites, and systematic discovery of induced structural changes without the need for compound modification or genetic engineering.
Clients provide cell pellets and compounds of interest, while Biognosys manages the complete workflow from sample preparation and LC‑MS acquisition to bioinformatics analysis and data interpretation. Each project begins with an in‑depth scientific consultation and is supported by a dedicated project manager. Results are reviewed in a final expert discussion to contextualize findings and translate them into actionable next steps.
Proteomics Service
TrueTarget enables high‑resolution, peptide‑level mapping of compound binding sites, revealing where and how a molecule engages its target in a native cellular context. The approach provides detailed insight into binding interfaces, conformational changes, and allosteric effects, delivering mechanistic and structural information that can directly inform structure–activity relationship (SAR) development.
Binding site mapping is particularly valuable for mechanistic characterization and lead optimization. Because experiments are performed in intact cells rather than on purified proteins, the approach is well suited to challenging targets, including proteins that form large or transient complexes, unstable proteins, and intrinsically disordered proteins that require a cellular environment to adopt functional conformations. The method is broadly applicable across mammalian, bacterial, and insect cell systems.
The service is typically performed using overexpression systems, in which the target protein is expressed at elevated levels in a cell line of choice. Experiments are conducted in a native cellular milieu to preserve physiologically relevant interactions and conformations. Biognosys delivers peptide‑level resolution of binding interfaces through a fully integrated workflow, providing interpretable, actionable results for downstream drug discovery efforts.
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