Hydrophobic Tag Services Profacgen

Despite the great progress in developing ligands to specific proteins, there are only about 300 molecular targets for approved drugs have been characterized. This indicates that a large fraction of the proteome can be considered “undruggable” by current technologies. Thus, finding therapeutic agents to treat disease-causing targets that are now thought to be undruggable will largely expand the boundary of the pharmaceutical arsenal.

A remaining challenge in small-molecule discovery is to determine whether the failure of a small-molecule inhibitor is due to unpredicted in vivo metabolism or whether it is simply due to the poorly selected target. This question can be answered, at least in part, by in vivo validation of the drug target, which generally requires a known inhibitor of the protein. Recently, a new technology termed “Hydrophobic Tag” has been discovered to enable small-molecule control over the target protein in the absence of a direct ligand, providing an ideal way to study and validate potential drug targets in various disease models. 1Hydrophobic Tag

Taking advantage of the hydrophobicity-driven nature of protein folding, hydrophobic tag intends to mimic protein misfolding by attaching a hydrophobic moiety to the surface of the target protein via either non- covalent interaction or HaloTag-induced conjugation. Partially folded or misfolded proteins can be recognized by other intracellular factors and will eventually undergo degradation to avoid excessive protein aggregation.

Indeed, developing a hydrophobic tag system for specific target proteins can be expensive and time-consuming, which might become an impediment for smaller companies and research institutes. As a leading CRO specialized in biotechnology and pharmaceutical sciences, Profacgen offers well-designed strategies to bend the cost and time curve of your research projects, and our risk management will ensure the maximum cost efficiency for our customers.

Our featured hydrophobic tag services currently include: HaloTag fusion protein: production of the target protein and HaloTag; purification of the recombinant product; protein activity evaluation. Synthesis of halogen-containing hydrophobic small molecules: design and synthesize hydrophobic fragments that are compatible with HaloTag-induced conjugation. Comprehensive analysis and method validation: all products are subjected to a full range of characterization at our analytical facility; the protein degradation will be tested using in vitro models. In vivo applications: the reliability and efficacy of the newly developed system are tested in vivo to bring ultimate confidence and satisfaction; potential drug targets can be identified both in cell lines and in animal models.

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