Proteins undergo a diverse array of post-translational modifications (PTMs) to their amino acid side chains, which strongly affect protein function and mediate intricate cellular events. Measuring the diversity, dynamics, and functional consequences of PTM states of proteins across the proteome is essential to understanding the role of proteins in health and disease. However, discovery and detection of PTMs and routine measurement of complex PTM states remains highly challenging and the diversity of proteoforms in the human proteome remains largely unmapped1. New, more sensitive methods for PTM detection will greatly aid biomarker discovery, drug discovery, and the development of precise and personalized approaches to medicine.
Modifications of the arginine side chain are of biomedical interest. Methylation and citrullination of arginine residues in human proteins have been shown to play key roles in disease states such as cardiovascular disease, autoimmune disease, and cancer. Here, we demonstrate the application of Quantum-Si’s next-generation protein sequencing™ technology to the detection of arginine methylation and citrullination in P38MAPKα and Vimentin proteins with single-molecule resolution and sensitivity. Quantum-Si’s PlatinumTM technology offers a sensitive platform for PTM detection and discovery with the power to address the critical need for accessible methods to study the role of PTMs in human health and disease.