NEW YORK, Oct 23 - Packard BioScience said Monday its wholly-owned subsidiary BioSignal Packard had entered into a $5.5 million proteomics contract with Astra Zeneca's R&D arm in St. Laurent, Quebec.
The contract follows a previous three-year agreement between the two companies to
conduct high-throughput screening for AstraZeneca's compounds. This agreement involved an initial $1 million research payment and undisclosed milestone payments.
Under the new agreement, AstraZeneca researchers will use BioSignal Packard’s new bioluminescence resonance energy transfer technology, or BRET 2 , to screen its library of combinatorial compounds against a group of G-protein-coupled receptors.
”In addition to revenue growth, the expanded agreement provides an excellent
opportunity to more broadly apply our recently introduced BRET 2 technology
for proteomics,” Daniel Chelsky, president of BioSignal Packard, said in a
AstraZeneca is the first company to publicly announce using BRET 2 in its research.
BRET 2 uses blue Renilla luciferase and a substrate, DeepBlueC, along with its green fluorescent protein, to test two proteins that are expected to interact with one another in a cell.
The luciferase and DeepBlueC, which emit blue light when combined, are attached to one protein, and the green fluorescent protein is attached to the other. When the luciferase and green fluorescent protein are close together, the green fluorescent protein will absorb the blue light and re-emit it as green light.
By measuring the proportion of blue light wavelengths to green light wavelengths emitted in this interaction between proteins, scientists can determine the distance at which the proteins interact and how long they interact.
BRET technology has advantages over traditional yeast-yeast based assays for
studying protein interaction, according to a January 5, 1999 article in the
Proceedings of the National Academy of Sciences . That article, by Vanderbilt University
biologist Yao Xu and his colleagues, said that BRET offers fewer cell-specific limitations and can more readily be used for high-throughput screening.
But the technology also has limitations, Xu warned. The proteins may interact in such a way that the luciferase and green fluorescent protein are not close enough to exchange light energy. Hence a negative result would not prove non-interaction. But this limitation is also present in other assays, he said.
AstraZeneca is combining this BRET technology, with a screening approach, “Focused Library Screening,” that it developed with BioSignal Packard. Focused Library Screening involves the rapid testing of a limited number of compounds against a panel of structurally diverse GPCR targets. AstraZeneca believes this screening process will help it quickly identify and develop drugs for defined targets.
”The Focused Library Screening program has accelerated our drug discovery operations,” Philippe Walker, vice president of discovery at AstraZeneca R&D, said in a statement. “With its broad target portfolio, efficient operation and emphasis on the development of new technologies, BioSignal Packard is a highly valuable partner.”