New York, USA – April 12, 2021 – An intact PROTAC molecule consists of a ligand for target proteins, a linker, and a ligand against E3 ubiquitin ligase. Though a wealth of research focuses on modification of the two protein-binding ligands, the linkers specifically are also the key to PROTAC drugs. Current evidence proves that the complete degradation efficiency of a PROTAC molecule does not only depend on the affinities of the E3 and POI but also on a suitable crosslinker for better POI ubiquitination.
Based on the opinion that all three components are indispensable for the efficiency of PROTAC drugs, in addition to ligands, Creative Biolabs spends much time and energy on PROTAC linkers design and optimization, ameliorating the linkers from types, locations, and chain lengths to provide more qualified linker products.
PROTAC Linker Types
There are a variety of linker types in the development of PROTAC. The most commonly used linkers for PROTAC ternary complexes formation are PEG (polyethylene glycol), alkyl-chain, and alkyl/ether.
These linkers grant rapid and facile assembly of potent degrader structures and some other key advantages to PROTAC molecules. For example, PEG-inserted linkers are highly water-soluble and non-immunogenic and are widely used in pharmaceutical and biotechnology research and development. Moreover, the diverse insertion of PEG and alkyl-chain also enables scientists to tune important physical properties of PROTAC molecules such as lipophilicity and cell permeability.
PROTAC Linker Locations
Studies revealed that the binding sites of ligands also play an important role in the efficiency of target degradation as the binding affinities may be altered when additional chemical structures are involved. Ligand-linker conjugate from Creative Biolabs is a solution to such issues, which enables to evaluate the properties of ligands and linkers simultaneously and share a close result with a complete PROTAC molecule.
PROTAC Linker Lengths
Evidence found a significant effect of chain length on the efficacy and the activity of PROTAC molecules, which means the distance between the E3 ubiquitin ligase and the target protein also matters. Taking advantage of an advanced chemical molecule design and synthesis platform, Creative Biolabs can fine-tune the linker length from 12-carbon to over 20-carbon to achieve maximal interaction, depending on the customer’s specific research need.
Learn more services for linker design and optimization and PROTAC linker products at https://www.creative-biolabs.com/protac.
About Creative Biolabs
Creative Biolabs has long been engaged in PROTAC molecule development. It has developed a comprehensive chemical molecule design and synthesis platform to design and optimize desired linker types, lengths, and positions. What’s more, to broaden the application of PROTAC drugs in different diseases, Creative Biolabs covers a wide range of linker products, including alkyl-chains, PEGs, and alkyl/ethers which are unanimously praised by clients from all over the world.