|This article may rely excessively on sources too closely associated with the subject, preventing the article from being verifiable and neutral. (October 2012)|
Enabling ubiquitin-based drug discovery
|Services||Custom ubiquitinated peptide synthesis, HTS assay reagent manufacturing|
UbiQ is a biotechnology enterprise based in Amsterdam, Netherlands. UbiQ originated from the Netherlands Cancer Institute (NKI). The company was founded based on discoveries in ubiquitin related research. The company commercializes several products and services incorporating these findings.
Custom ubiquitinated peptide synthesis
UbiQ-PEP is a custom peptide synthesis and site specific ubiquitination service. Production is based on Solid phase peptide synthesis. Based on proprietary technology UbiQ offers conjugation of ubiquitin on any position starting at low yields for research applications. Typical fields of research where these peptides are applied include:
- Antigen processing
- Apoptosis and proteolysis
- Immune response and inflammation
- Muscular and neural degeneration
- Morphogenesis of neural networks
- Modulation of cell surface receptors, ion channels and the secretory pathway
- Response to stress and extracellular modulators
- Viral infection
HTS assay reagents
In collaboration with pharmaceutical companies UbiQ develops and manufactures high throughput screening assay reagents. UbiQ is mostly involved in isopeptide-based assays as tools for Deubiquitinating enzyme inhibitor drug discovery.
UbiQ has developed and manufactured several frequently used ubiquitin related reagents for commercialization. These reagents are typically available through third party suppliers such as Boston Biochem Inc. and LifeSensors.
The UbiQ technology relies on three basic concepts, UbiQ-Block, UbiQ-Click and UbiQ-Syn. These chemical synthesis technologies allow manufacturing of Ubiquitin conjugates, Ubiquitin mutants and combinations thereof.
UbiQ-Block is a chemical ligation approach that allows construction of Ubiquitin and/or Ub-like protein (Ubl) modified polypeptides. Some applications of these Ub/Ubl modified polypeptides include:
- as reagents in the search for inhibitors of deubiquitinating enzymes (DUBs)
- to perform deubiquitinating enzyme activity profiling
- in the development of antibodies (quality control)
UbiQ-Click technology enables synthesis of proteolytically stable Ubiquitin modified (poly)peptides. Here the native isopeptide bond is replaced by a proteolytically stable amide isostere. These conjugates can be used:
- for immunization experiments with modified peptide antigens
- as affinity support in Mass spectrometry based proteomics studies
- in deubiquitinating enzyme affinity studies
UbiQ-Syn is a solid phase peptide synthesis of the 76 amino acid Ubiquitin polypeptide sequence. It allows production of Ubiquitin mutants. These Ubiquitin mutants can be used:
- to study Ubiquitin-protein interactions
- as intermediates of special products (e.g. radioactive labelled Ubiquitin)
- Geurink, P. P.; El Oualid, F.; Jonker, A.; Hameed, D. S.; Ovaa, H. (2012). "A General Chemical Ligation Approach Towards Isopeptide-Linked Ubiquitin and Ubiquitin-Like Assay Reagents". ChemBioChem 13 (2): 293–297. doi:10.1002/cbic.201100706. PMC 3488293. PMID 22213387.
- Chemical Synthesis of Ubiquitin, Ubiquitin-Based Probes, and Diubiquitin F. El Oualid et al. Angew. Chem. Int. Ed.2010, 49, 10149 10153.PMID 21117055
- Thiolysine and selenolysine building blocks and their use in site-and chemoselective modification of peptides and proteins WO2010131962A2, PCT/NL2010/050277, US61/176,616, EP09160430.6
- Total chemical synthesis of ubiquitin, ubiquitin mutants and derivatives thereof US61/383,029
- Non-hydrolyzable protein conjugates, methods and compositions related thereto. US61/353,780, US61/351,659
- Synthesis and characterization of fluorescent ubiquitin derivatives as highly sensitive substrates for the deubiquitinating enzymes UCH-L3 and USP-2. Tirat et al., Anal. Chem. 2005, 343, 244255. PMID 15963938