Abstract
The peptidome represents the array of endogenous peptides that are present in both the intracellular and extracellular space of the body. Peptides are constantly generated in vivo by active synthesis, and by proteolytic processing of larger precursor proteins, often yielding protein fragments that mediate a variety of physiological functions. Given that aberrant proteolysis is a hallmark of various pathological diseases, many studies have now turned to the peptidome. Differential regulation of endogenous peptides may play a role in many pathological conditions. Mass spectrometry (MS) -based investigation of peptides in a system-wide manner is currently facilitating the identification of potential biomarkers. Furthermore, peptidomic approaches have provided major contributions to the identification of protease-substrate relationships; representing one of the major challenges in understanding and therapeutically exploiting protease function in health and disease. As such, degradomic studies looking for cleavage products via peptidomics in particular, have warranted a significant research interest in recent years. Given that substantial studies are accumulating in the field of peptidomics, this review highlights recent advances of MS-based peptidomic strategies in facilitating the identification of potential peptides as novel clinical markers and protease-substrate profiling.
About the authors
Zon Weng Lai received his PhD training at the Monash Biomedical Proteomics Facility, Monash University, Victoria, Australia. His initial post-doctoral training at the Clinical Biomarker Discovery and Validation team at Monash University focused on the establishment of multi lectin-based chromatography for glycoproteomics studies. He has recently taken up a Marie Curie International Incoming Fellowship, training at the Institute for Molecular Medicine and Cell Research, Freiburg, Germany. His main research focuses on the establishment of novel methods for clinical proteomics and mass-spectrometry-based identification of novel targets as potential markers for diseases.
Agnese Petrera completed her PhD degree at the Life Science Zurich Graduate School at the University of Zurich, Switzerland. Currently, she is training as post-doctoral fellow at the Institute for Molecular Medicine and Cell Research, Freiburg, Germany. Her main research interests evolve around the application of proteomic approaches to cardiac pathologies aiming to profile alterations in the cardiac proteome under different stress conditions. She is involved in a joint research project with Sanofi-Aventis GmbH to characterize the role of cathepsin A inhibition as a novel target for heart failure.
Oliver Schilling is an Emmy-Noether group leader and ERC grantee at the University of Freiburg, Institute of Molecular and Medicine. He studied Biology in Germany and France and pursued his PhD studies at the European Molecular Biology Laboratory. Afterwards, he joined the laboratory of Prof Christopher M. Overall at UBC, Vancouver, Canada for postdoctoral training. Oliver’s laboratory focuses on degradomic studies to better understand the role of proteolysis in health and disease.
Acknowledgments
O.S. is supported by grants of the Deutsche Forschungsgemeinschaft (DFG) (SCHI 871/2 and SCHI 871/5) and the SFB850 (project B8), a starting grant of the European Research Council (Programme ‘Ideas’ – Call identifier: ERC-2011- StG 282111-ProteaSys), and the Excellence Initiative of the German Federal and State Governments (EXC 294, BIOSS). Z.W.L. acknowledges a Marie Curie IIF fellowship (Call Identifier: FP7-PEOPLE-2012–11 F).
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