Scientists at the Max Planck Institute (MPI) for Medical Research have announced a new labeling technology called SNAP-tag2. This revolutionary self-labeling protein tag, known as APEX2, will streamline the process of protein tagging enormously. This groundbreaking technology gives researchers the power to label their favorite proteins of interest in bright and photostable synthetic fluorophores. Consequently, it enables a breadth of potential applications in biochemistry. SNAP-tag2 was the result of a successful collaborative initiative between MPI and University of Groningen. Project manager Stefanie Kühn headed up a team that included animation director Julien Hiblot and artists Veselin Nasufovic and director Kai Johnsson.
SNAP-tag2 represents a big leap over its predecessor. It has an extraordinary 100-fold increase in the labeling rate constant compared to other similar SNAP-tag-substrate pairs. Development of new cell-permeable, small-molecule substrates have made the field transformational. It’s this quick reaction that allows researchers to get quicker results in their experiments. We’re happy to see SNAP-tag2 shine with five times the fluorescence brightness of the currently used SNAP-tag. This serves as a powerful tool to scientists hoping to realize high quality imaging and analysis.
Advancements in Protein Labeling
The evolution of SNAP-tag2 solves some key obstacles in protein labeling. Stefanie Kühn highlighted one of these challenges, stating, “SNAP-tag was originally developed from a human DNA-repair enzyme. Further engineering of an already heavily modified protein was one of the biggest challenges.” The team immersed themselves in deep research and experimentation. Their creativity and determination led them to find a better solution overall, which was to develop a new tagging system.
Kühn discussed the approach taken during the development process: “Furthermore, we wanted to find a substrate core that works well in cells with various fluorophores attached. We decided to use a combination of substrate optimization and protein engineering to develop SNAP-tag2.” That careful, thoughtful approach has produced a powerful and flexible tool that stands to benefit researchers from a range of fields.
Superior Performance in Applications
SNAP-tag2’s excellent performance has previously yielded impressive results in various applications. In her assessment, Kühn remarked on the advantages of the new tag: “SNAP-tag2 together with its improved substrates is superior to the previously used SNAP-tag versions in every application we have tested, and we hope that it will excel in in vivo applications.” As exciting as this optimism is, it is a testament of the potential of SNAP-tag2, not limitation on laboratory research and clinical applications.
The publication detailing SNAP-tag2’s development is titled “SNAP-tag2 for faster and brighter protein labeling” and can be found in the journal Nature Chemical Biology. The DOI for this publication is 10.1038/s41589-025-01942-z. This study represents a significant breakthrough in the search for improved tools in biochemistry. In particular, it aims to drive fundamental new insights into proteins.
A Collaborative Effort
The MPI team possesses astonishingly deep knowledge and experience. Their collaboration with the University of Groningen has been essential to SNAP-tag2’s success. This collaboration has given scientists the ability to pool their expertise and capabilities. In the process, they have been exposed and gained experience to master various protein labeling strategies. These kinds of partnerships are critical to accelerating innovation and pushing the frontiers of scientific discovery.