Transcreener
Transcreener® Technology
Transcreener is a universal, high throughput biochemical assay platform based on detection of nucleotides, which are formed by thousands of cellular enzymes- many of which catalyze the covalent regulatory reactions that are central to cell signaling and represent new opportunities for therapeutic intervention. Transcreener uses far red FP, FI and TR-FRET which overcome compound interference.
Available Transcreener Assays include:
The Transcreener® ADP2 Assay is a new assay, with greater sensitivity than the original Transcreener ADP Assay. The improvement is a more sensitive antibody against ADP yielding an excellent signal at less than 10% ATP consumption for a broad range of initial ATP concentrations (0.1-1,000 μM). This assay is appropriate for the detecion of any enzyme class that produces ADP including protein, lipid, and carbohydrate kinases, triphosphatases, ATPases, DNA helicases, carboxylases and glutamine synthetase. The Transcreener ADP2 Assay is available in fluorescence polarization (FP), fluorescence intensity (FI), and time-resolved Förster-resonance-energy-transfer (TR-FRET) detection modes. All three emit in the red spectrum to minimize interference from fluorescent compounds and light scattering.
The Transcreener® AMP/GMP Assay for the detection of any enzyme class that produces either AMP or GMP, including ubiquitin, SUMO, nucleic acid and protein ligases, phosphodiesterases (PDEs), and synthetases.
The Transcreener® GDP Assay for the detection of any enzyme class that produces GDP, including GTPases.
The Transcreener® UDP Assay for the detection of any enzyme class that produces UDP, including protein, hepatic and glycoprotein UDP-glycosyltransferases (UGTs), glycosyltransferases and hyaluronan synthase.
Note: The Transcreener® ADP TR-FRET Assay is a competitive, time-resolved fluorescence resonance energy transfer (TR-FRET) assay for detection of ADP using the TR-FRET method and offers an additional method to scientists interested in ADP assays.
"Click here for valuable instrument optimization information."
The Drug Discovery Challenge
Most diseases are caused by malfunction of one of the more than 20,000 types of proteins in the human body. Developing effective drugs to treat a disease is a matter of finding molecules that disrupt the pathological effects of the aberrant protein – known as the “drug target” – without interfering with the normal function of related proteins. This is done through a process called High Throughput Screening (HTS), in which hundreds of thousands of potential drug molecules are tested for their interaction with a drug target. HTS has become the cornerstone of drug discovery, and pharmaceutical companies are under tremendous economic pressure to screen more new drug targets. However, development of assays for these targets is not keeping pace, and this has created a bottleneck in the drug discovery pipeline.
BellBrook Labs has developed a universal assay technology called Transcreener HTS Assay Platform that enables seamless incorporation of hundreds of new drug targets into HTS. The Transcreener HTS platform relies on a proprietary fluorescence detection method for group transfer enzymes that enables an entire family of enzymes to be screened using the same detection reagents. The Transcreener platform is unique in this regard; there is no other HTS platform with the potential to eliminate so much costly assay development for so many drug targets.
Group transfer reactions, such as phosphorylation and glycosylation, serve as important on/off switches for signaling proteins in diverse disease pathways. The stability and activity of small molecules, including drugs and hormones, is also controlled by group transfer reactions such as glucuronidation, methylation and sulfation. The enzymes that catalyze these reactions are generally assayed by detecting the covalently modified product; e.g. a phosphorylated peptide for kinase reactions. However, because the enzymes within a group transfer family have diverse substrate selectivity, this approach requires development of new detection reagents to move new family members into HTS.
Examples of group transfer enzyme familes.
| Target Family | Donor / Donor Product | Acceptors | Disease Areas |
|---|---|---|---|
| Kinases (>650) | ATP to ADP | Proteins | Cancer, Inflammation, Diabetes, Cardiovascular, Neurological |
| PDEs, ligases, synthetases | ATP to AMP cAMP /cGMP to AMP/GMP |
Proteins, lipids, small molecules | Inflammation, CNS, Hypertension, Sexual dysfunction |
| Glycosyltransferases (>200) | UDP-Sugar to UDP | Proteins, small molecules, DNA, RNA | Drug Metabolism, Cancer, Antimicrobials |
| Sulfotransferases (>50) | PAPS to PAP | Proteins, small molecules | Drug Metabolism, Cancer, Cardiovasular, Neurological, |
| Methyltransferases (>50) | SAM to SAH | Proteins, small molecules | Drug Metabolism, Cancer, Neurological |
| Acetyltransferases (>10) | Acetyl-CoA to CoA | Proteins, DNA | Drug Metabolism, Cancer |
Advantages of Transcreener Technology:
- Eliminating months of delays in moving new targets into HTS, with significant R&D cost savings.
- Accelerating the pursuit of new therapeutic strategies for cancer and other grievous diseases.
- Improving the ability to avoid adverse side effects, which cause almost half of all clinical failures.
- Improving the ability to develop more selective drugs by standardizing HTS methods and data across entire families of drug targets.
