Combinatorial Domain Hunting

DNA helix: protein manufacturing from Domainex

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The availability of sufficient protein of good quality can be rate limiting for many drug discovery programmes, as a lack of target protein supply can hamper the ability to establish hit screening assays and to gain structural information.

In situations where the target of interest is a challenging protein to produce, poor choice of expression construct is often the cause and standard bioinformatics approaches to construct design are unlikely to be suitable. This is because, while bioinformatics can enable good prediction of the conserved regions within a gene, these regions do not always translate into the best protein constructs for production in E. coli. In these cases, Domainex's proprietary high throughput Combinatorial Domain Hunting (CDH) approach can overcome this issue, by enabling the fast screening of over 100,000 different constructs of your protein domain of interest!

Domainex's technology has been used successfully to deliver stable, soluble protein for a range of target classes including, but not limited to:

  • Kinases
  • DUBs
  • Proteases
  • Protein methyltransferases
  • Demethylases

CDH

CDH is the unique, patented technology for quickly identifying soluble, highly expressible constructs of drug target proteins, which exhibit secondary structure formation and are suitable for use in structural studies and assay development. This results in the ability to develop drug target binding or activity assays and to complete compound screening within exceptionally fast timelines.

CDH combines a method for the production of unbiased finely-sampled gene-fragment libraries, with a screening protocol that provides 'holistic' readout of solubility, molecular weight and relative expression levels, for up to 120,000 protein domain constructs.

CDH has an established pedigree: over 50 genes have been studied to date, including projects for many of the 'Top 20' global pharmaceutical companies (click here to view UCB press release on successful use of CDH technology) and large biotech.

The construct selection process takes only three months, with an additional one to two months for protein purification. This can significantly de-rate limit early discovery phase programmes. Following construct selection from >100,00 possible varients, the 5 optimal protein constructs can be produced using E. coli or baculoviral expression systems; as is deemed necessary.

Click here to download factsheet

For more information regarding Domainex’s CDH drug discovery technology platform, please contact us at enquiries@domainex.co.uk.

Relevant publications relating to this technology can be found by clicking here.