Proteolysis Targeting Chimeras Research Based on SPR Technology

Proteolysis targeting chimeras (PROTAC) are heterodimeric bifunctional small molecules consisting of a target protein ligand, a linker, and an E3 ligase ligand, in which the two ligands are linked by the linker to form a trimeric polymer called the target protein ligand-linker-E3 ligand. PROTAC specifically degrades target proteins by bringing them closer to the intracellular E3 ubiquitin ligase, using the ubiquitin-proteasome pathway. Protein degradation is also an important expression of protein involvement in the physiological activities of living organisms. Living organisms rely on the continuous synthesis of proteins and the degradation of abnormal proteins to maintain proteome homeostasis. The ubiquitin-proteasome system is the primary pathway for 80% of protein degradation in living organisms. The ubiquitin-proteasome system is a multi-step reaction process involving many different proteins. In this process, proteins are first labelled with ubiquitin (polypeptides) before they are recognised and degraded by the proteasome. Through such an energy-intensive process, cells are able to degrade unwanted proteins in a highly specific manner. The ubiquitin-proteasome system consists of ubiquitin (Ub), ubiquitinactivating enzyme (E1), ubiquitinconjugating enzyme (E2), ubiquitin The ubiquitin-protein ligase (E3), the proteasome and its substrate (protein). The ubiquitin-protein ligase system is an important regulator of a range of intracellular life processes and is closely linked to the development of disease. In contrast to the traditional approach of inhibiting target protein activity by developing target protein inhibitory molecules, PROTAC requires only highly selective binding to its targets. This is why many researchers are currently working to transform previously ineffective inhibitor molecules into next generation PROTAC drugs.

Fig.1 The schematic diagram of the small molecule - based on the PROTAC. The PROTAC consists of a ligand on an E3 ubiquitin ligase, a linker, and a ligand on targeted protein. (Zou, Y, et al., 2019)

Surface plasmon resonance (SPR) in the process of proteolysis targeting chimeras research

In order to maintain the proteomic balance of the living organism, some of the proteins are degraded while the living organism is constantly producing new ones. The ubiquitin proteasome is an important pathway for the degradation of proteins. Based on this protein degradation pathway, if we can achieve selective degradation of abnormal proteins, this could be a new direction for the development of drugs for disease treatment. In this way, Proteolysis targeting chimeras could be a new direction for the study of targets that are not druggable. If you have a related research need, please consider looking at our SPR technology platform, which can provide high-throughput screening for protein-small molecule interaction analysis in your PROTAC studies. The general flow is shown in the diagram below. The high throughput nature of SPR technology allows hundreds of samples to be screened simultaneously in a single run, saving time and reducing costs. No one should be able to resist such efficient molecular interaction analysis. What's more, the high sensitivity of SPR technology ensures a high degree of data accuracy at very low molecular weights by significantly reducing the detection limit. With this in mind, you can be confident that the results from our SPR technology platform will allow you to move forward with the development of drugs for protein variant-related diseases. As you can see, our SPR technology platform is far more efficient than traditional molecular interactions, and you definitely deserve it.

Fig.2 The SPR technology platform in the process of proteolysis targeting chimeras research

As you can see from the above, we believe that you have a good idea of the benefits of the SPR technology platform for protein-small molecule interaction analysis in PROTAC research. If you have any further questions, please do not hesitate to contact us for more detailed answers. All services in Creative Proteomics, please keep in touch with us at any time.

For research use only. Not intended for any clinical use.