Exploiting Selective Position Labeling to Unveil the Hidden Complexity of Terminomics

Area of Science:

• Biochemistry and Molecular Biology
• Proteomics
• Chemical Biology

Background:

• Selective protein terminal labeling is vital for understanding proteolytic mechanisms in disease.
• Protein termini offer insights into functional proteome states but are often low in abundance.
• Terminomics, the study of protein termini, requires highly selective labeling approaches.

Purpose of the Study:

• To review recent advances in N-/C-terminal modification strategies for terminomics.
• To evaluate modern chemical and chemoenzymatic methods for site-specific protein labeling.
• To highlight emerging strategies for enhanced substrate adaptability and reaction efficiency.

Main Methods:

• Review of recent literature on N-/C-terminal protein modification.
• Evaluation of chemical and chemoenzymatic labeling techniques.
• Analysis of strategies leveraging engineered reactivity or enzymatic precision.

Main Results:

• Advances in N-/C-terminal modification strategies are enabling precise tracking of cleavage dynamics and protease interactions.
• Modern methods offer enhanced selectivity and efficiency for labeling low-abundance protein termini.
• Emerging strategies demonstrate improved substrate adaptability, reaction efficiency, and workflow compatibility.

Conclusions:

• Selective protein terminal labeling is essential for system-wide studies of proteolytic mechanisms.
• Recent advances in chemical and chemoenzymatic methods significantly advance the field of terminomics.
• Emerging strategies promise broader applications in analyzing cellular networks and proteolytic events.