TAILS Proteomics
TAILS proteomics (Terminal Amine Isotopic Labeling of Substrates) is a high-resolution proteomic strategy designed to characterize the structural features of protein N-termini and to identify protease cleavage sites. This approach involves chemical labeling of protein N-terminal amines using isotopic reagents, followed by selective enrichment and mass spectrometry analysis, enabling sensitive and systematic detection of both native N-termini and neo-N-termini generated by proteolytic processing. In contrast to conventional proteomics, which primarily focuses on changes in protein abundance, TAILS proteomics emphasizes the detection and characterization of proteolytic processing events themselves. This makes it particularly useful in functional studies of proteases, many of which play central roles in cell signaling, metabolic homeostasis, and pathological responses, often exerting their biological effects through substrate-specific cleavage. TAILS enables high-throughput identification of such cleavage events, allowing researchers to delineate the molecular pathways regulated by proteases. TAILS proteomics has also emerged as a valuable tool in drug discovery. By comparing proteolytic profiles before and after compound treatment, researchers can assess the effects of candidate drugs on protease-substrate interactions, thereby revealing mechanisms of action or potential off-target effects. This is especially important in the development of protease inhibitors, antibody-drug conjugates, and protein degradation-based therapies such as PROTACs. The cleavage site information obtained through TAILS is indispensable in these contexts. Furthermore, TAILS proteomics can be applied to evaluate protein stability, monitor protein half-life, and trace degradation pathways, thus providing strong support for the advancement of targeted protein degradation therapies.
The core workflow of TAILS proteomics consists of three main steps: (1) blocking or chemically labeling free amine groups in protein samples to prevent undesired reactions; (2) applying specific enrichment strategies to isolate N-terminal peptides from complex proteomes; and (3) performing high-resolution mass spectrometry for peptide identification and quantification. This workflow significantly enhances both the specificity and throughput of N-terminal analysis, facilitating the capture of subtle, transient, or low-abundance proteolytic events. Using TAILS proteomics, researchers can reconstruct the substrate landscape of proteases under specific physiological or pathological conditions, thereby providing robust datasets for mechanistic insights and therapeutic target validation.
In terms of experimental execution, TAILS proteomics requires stringent control over sample purity, chemical labeling efficiency, and mass spectrometry parameters. Depending on the research objective, different labeling strategies such as dimethyl-TAGS or SILAC-TAILS can be employed. Data interpretation involves integration of protein sequences, N-terminal identification sites, protease recognition motifs, and the functional context of cleavage sites, enabling the construction of comprehensive protein processing regulatory networks. As such, TAILS proteomics functions not only as an experimental platform but also as a critical component in systems biology, bridging structural proteomic alterations with functional regulatory mechanisms.
With deep expertise in proteomics technologies, MtoZ Biolabs is committed to delivering integrated and high-quality N-/C-terminal sequencing services tailored to clients' research needs.
MtoZ Biolabs, an integrated chromatography and mass spectrometry (MS) services provider.
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