A sunny solution

Cisbio partners with Blue Sky to target kinases

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PARIS—Cisbio Bioassays has agreed to partner with Blue Sky BioProducts of Worcester, Mass., in a joint effort that will combine Cisbio's homogenous time-resolved fluorescence (HTRF) technology with Blue Sky's TDA 2.0 technology—a stable solution of lipid-based nanoparticles with nickel-chelating moieties.

"In order to rapidly and efficiently interrogate chemical libraries, in vitro homogenous assays are usually developed," notes Blue Sky's Dr. Scott Gridley, director of the company's BioProducts division. "When the enzyme of interest is naturally membrane associated, it has been necessary to remove the protein from the membrane and ignore all of the properties that membrane association confers to that enzyme, such as polarity, topology and relationship to other subunits. The alternative has been to assay the enzyme in intact cells, which is slow and costly. Template-directed assembly is the process of building a cell-like context for enzymes of interest in vitro. Our patented reagent, TDA 2.0, makes this process simple, allowing for development of high-throughput screens with the biological fidelity of a cell-based assay, revolutionizing the way drugs will be discovered for membrane-associated enzymes."

The combination of TDA 2.0 and Cisbio's HTRF will enable the development of more robust assays that the partners believe will provide an unparalleled sensitivity for obtaining better biologically enhanced results on target kinases.

"Through HTRF, Cisbio has developed extensive expertise in the field of kinase enzyme screening tools," explains François Degorce, director of marketing and communications at Cisbio Bioassays. "The combination of these two proven technologies in this area allows us to provide an even more robust and efficient solution for studying these key therapeutic targets, particularly in oncology research."

The HTRF platform offers a broad choice of reagents and kits for high-throughput screening of kinases, whether Tyrosine (Tyr) or Serine/Threonine (Ser/Thr). Researchers have a universally applicable technology for screening and studying major human kinome targets and an economical solution in terms of implementation and development time, Degorce adds.

TDA 2.0 is a is a template which directs the assembly of purified polyhistidine- (His) tagged proteins that are normally membrane-associated, creating a more physiological environment than isolated domains in aqueous buffer. His-tagged proteins bind to the fluid surface of TDA 2.0 and self-associate as a result of the fluid properties of the lipid bilayer. Use of TDA 2.0 is straightforward and significantly less challenging than traditional membrane reconstitution procedures. Membrane protein assays developed in conjunction with TDA 2.0 exhibit dramatic increases in enzymatic activity, improved physiological buffer compatibility, and a preference for biologically relevant substrates, Gridley states.

"Template-directed assembly using TDA 2.0 is an exciting advancement that provides researchers with a simple tool to develop HTS assays that more closely mimic physiological conditions than can be achieved with isolated catalytic domains," he adds. "Performing assays with membrane-associated kinases using TDA 2.0 in combination with HTRF detection enables unparalleled results."

Cisbio's Degorce notes that for the moment, each company will continue to be responsible for its own technology. A co-marketing agreement will facilitate cross-training of customers to demonstrate how the two technologies are compatible and the results that can be expected from using them in tandem. Degorce notes that Cisbio and Blue Sky already have customers in common who should benefit from the partnering agreement. SmartScreen kits containing TDA 2.0 developed by Blue Sky BioProducts offer a pre-validated, high-quality enzyme, substrate and reaction buffers that are particularly suitable for HTRF technology, Gridley adds.

Cisbio Bioassays is a member of the IBA Group and is a global provider of HTRF technology and services to facilitate new drug discovery. The company has a U.S. subsidiary in Bedford, Mass. 

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