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Application Biopharma Drug Targets

Antibiotic drug discovery – synthesizing a panel of drug targets

The Problem

Drug targets are an essential component of any drug development campaign, but oftentimes they are difficult to access.

The Tierra Solution

With Tierra’s Protein Platform, drug developers can now order panels of drug targets with ease and receive purified proteins in as little as 3 weeks.

One major challenge in drug discovery efforts is the difficulty of producing panels of drug targets for lead identification and optimization. Scientists must produce or procure multiple targets, which can be a challenge if the target proteins are hard to find commercially at the quality needed for testing. With recombinant cellular protein synthesis, scientists can spend months trying to synthesize targets and might produce only a small fraction of all the targets they would like to test. Recombinant cellular methods also struggle to produce drug targets with multiple sub-domains, where optimization of each domain is challenging. Ultimately, this leads to painfully long drug development timelines and missed opportunities due to the abandonment of difficult-to-express candidates.

With Tierra’s Protein Platform, drug developers can now order panels of drug targets with ease and receive purified proteins in as little as 3 weeks. As a case study, Tierra’s platform was used to synthesize a panel of 47 Acinetobacter baumannii (Ab) protein targets. Acinetobacter is bacteria that are increasingly resistant to antibiotics, and for which new drugs are needed. To support these efforts, Tierra attempted synthesis of this panel to see if active targets could be produced for further development.

From this attempt, Tierra was able to produce all 47 bacterial drug targets attempted as validated by SDS-PAGE gels. To validate activity, a subset of the targets produced are penicillin-binding proteins (PBPs) and are known to bind penicillin when properly folded and active. We incubated these PBPs with a fluorescent derivative of penicillin, Bocillin, and measured the fluorescence of the bound samples. Each PBP bound Bocillin. This data confirms the targets produced were properly folded, active targets. Tierra has also produced diverse prokaryotic and eukaryotic drug targets, including those that are disulfide-bridged and hard to make using E. coli recombinant methods.

With quality drug targets being one of the major bottlenecks in drug discovery programs, rapid production of protein targets reduces time for lead identification and optimization. Tierra Protein Platform completes production of large drug target panels in as little as 3 weeks. Targets can be produced at the microgram scale or milligram scale to enable larger screens and panning campaigns. For more complex projects featuring multi-subunit protein complexes or proteins with known necessary co-factors, contact us to see how we can help on our custom platform.


Expression Data

Binding Data

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