The emerging proteolysis-targeting chimera (PROTAC®) technology provides a highly promising new modality for drug discovery and is capable of reaching beyond the boundaries posed by traditional drug discovery. As a leading contract organization, Creative Biolabs is capable of offering comprehensive drug discovery services to promote the development of global researchers’ programs. Particularly, we provide ligand design services to construct X-protein-targeting PROTAC® for our clients.
X-protein is a non-structural protein encoded by the hepatitis B virus (HBV). Studies have shown that X-protein plays a key role in gene transcription, intracellular signal transduction, genotoxic stress response, protein degradation, cell cycle control, apoptotic cell death, and carcinogenesis. Also, X-protein could stimulate HBV replication by activating viral transcription and enhance viral polymerase activity via calcium signaling pathways. Moreover, it has been reported that X-protein contributes to the development of HBV-induced hepatocellular carcinoma (HCC). Therefore, X-protein could be treated as a potential new drug target for the treatment of HBV.
Fig.1 X-protein-induced epigenetic modifications of active and repressed host genes. (Tian, 2013)
X-protein consists of 154 amino acids (aa) and has a molecular mass of approximately 17 kDa. Generally, PROTAC®s consist of a ligand capable of binding the target protein, fused to a peptide (referred to as the degron) that is recognized and polyubiquitinated by an E3 ligase. As to X-protein, the instability domain of the X-protein could serve as a novel E3 ligase recognition signal (degron). Thus, the PROTAC® non-covalently binds to X-protein and recruits E3 ligase via the degron peptide, which results in polyubiquitination and degradation of X-protein. To date, peptide targeting X-protein has been used for PROTAC® construction to treat HBV infection and the development of HCC.
Regions of the X-protein that are polyubiquitinated and susceptible to degradation lie within the middle of the protein at aa 52-102, and also within the instability domain at aa 103-154. Based on the specific structural characterization of X-protein, Creative Biolabs is able to develop numerous ligands for X-protein-targeting PROTAC® development. With our advanced technology platforms and experienced scientists, we are able to promote your project success using a variety of strategies, including but not limited to structure-based computational screening methods and phage display based recombinant antibody construction. Moreover, we also provide ligand modification and optimization services of existing ligands with better affinity and cell penetrability.
As a pioneer company in small molecule candidate discovery and development, Creative Biolabs is committed to providing high-quality ligand design and synthesis services to promote the exploration of novel small molecules. Based on our advanced PROTAC® platform, we are confident in presenting a full package of services to promote your program a success. If you are interested in the services we provide, please feel free to contact us for more detailed information.
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