Exploring Bioactive Peptides: From Immune Defense to Obesity Treatment
April 4, 2025 • Meredith Carpenter, PhD
April 4, 2025 • Meredith Carpenter, PhD – Head of Scientific Affairs
Bioactive peptides have recently entered the spotlight in biomedical research due to their growing number of physiological roles1. These naturally occurring molecules are involved in everything from immune responses to metabolism, making them prime candidates for therapeutic interventions. As scientists continue to explore the hidden potential of bioactive peptides, some fascinating recent discoveries are showing just how versatile and powerful these tiny molecules can be.
One area of significant interest is the role of bioactive peptides in the immune system. For years, proteasomes—complex molecular machines responsible for degrading proteins in cells—were primarily understood as being involved in antigen presentation. They break down proteins into small peptides, which are then displayed on the surface of cells to alert the immune system to potential threats. However, a recent study has uncovered an additional, crucial function for proteasome-derived peptides: acting as part of the body’s first line of defense against bacterial infections2.
This study revealed that the proteasomes not only generate peptides for immune signaling but also produce antimicrobial peptides that directly fight pathogens. These antimicrobial peptides, produced both constitutively and in response to bacterial infections, disrupt bacterial membranes, preventing the growth and spread of harmful microorganisms. In silico analysis predicted hundreds of thousands of potential antimicrobial peptides, suggesting that the proteasome’s role in innate immunity is far more expansive than previously thought.
This discovery paves the way for new therapeutic interventions, particularly in the realm of infectious diseases and conditions where the immune system is compromised. By tapping into the body’s natural production of defense peptides, we may find novel ways to fight infections, potentially bypassing some of the resistance issues seen with traditional antibiotics.
Bioactive peptides are also showing promise in the treatment of obesity. In a different study, researchers used computational drug discovery to systematically map more than 2,600 previously uncharacterized human proteolytic peptide fragments, enabling the identification of novel bioactive peptides3. As part of this effort, they identified a novel peptide, the BRINP2-related peptide (BRP), that reduces food intake and promotes weight loss in animal models without triggering side effects like nausea or aversion. Unlike other appetite-regulating treatments that act through familiar pathways such as leptin or GLP-1 receptors, BRP works by activating central FOS signaling, a protein involved in the brain’s hunger regulation. This distinct mechanism may lead to obesity treatments that are both effective and well-tolerated.
The identification and analysis of bioactive peptides, however, come with their own set of challenges. One of the primary methods for detecting peptides is mass spectrometry (MS), which is invaluable for peptide profiling. However, mass spectrometry has some limitations, particularly when it comes to accurately detecting and quantifying these short peptides. For example, MS can struggle to detect peptides that are present in low abundance, have highly similar masses, or have poor ionization properties.
Next-Gen Protein Sequencing™ (NGPS™) on the Quantum-Si Platinum® Pro instrument offers a promising solution to these challenges. This technology is capable of sequencing proteins at the single-molecule level, offering high sensitivity, accuracy, and the ability to identify peptides may be overlooked by traditional methods like mass spectrometry. By unlocking a more complete understanding of the peptide landscape, advanced sequencing tools like NGPS could accelerate the discovery of new therapeutic peptides, providing more targeted and effective treatments for diseases ranging from infections to metabolic disorders.
References:
1Foreman, R. E., George, A. L., Reimann, F., et al.. Peptidomics: A Review of Clinical Applications and Methodologies. Journal of Proteome Research 20 (8), 3782-3797 (2021). https://doi.org/ 10.1021/acs.jproteome.1c00295
2Goldberg, K., Lobov, A., Antonello, P. et al. Cell-autonomous innate immunity by proteasome-derived defence peptides. Nature 639, 1032–1041 (2025). https://doi.org/10.1038/s41586-025-08615-w
3Coassolo, L., B. Danneskiold-Samsøe, N., Nguyen, Q. et al. Prohormone cleavage prediction uncovers a non-incretin anti-obesity peptide. Nature (2025). https://doi.org/10.1038/s41586-025-08683-y
Meredith Carpenter, PhD, Head of Scientific Affairs, Quantum-Si
Meredith L. Carpenter, PhD, is head of scientific affairs at Quantum-Si, where she manages external collaborations and publication strategy. Dr. Carpenter has over 10 years of experience in developing and deploying novel genomics and multi-omics tools in the biotech industry. Prior to Quantum-Si, Dr. Carpenter held roles as director of assay development at Arc Bio and senior director of strategic alliances at Cantata Bio. She earned a BS in Biology from Emory University and a PhD in Molecular and Cell Biology from UC Berkeley, and she performed postdoctoral research in the Department of Genetics at Stanford University.