Chaperone screens for DnaK inhibitors

SCRANTON, Pa.—Chaperone Technologies Inc. is using its antimicrobial drug discovery assay system to screen potential drug candidates from the National Institutes of Health's library of compounds.

The open-ended collabora-tion, implemented through the NIH's Molecular Libraries Screening Center Network location at Emory University, requires adapting Chaperone's system for high-throughput screening. "One of the first [program benefits] is the validation of DnaK as a target," says Chaperone CEO and president Ken Kovan. "And there's certainly a tremendous amount of value in that, having the NIH endorse what we're doing. The second point is the scaling up of the assay itself."

Chaperone is investigating candidates that inhibit DnaK, a bacterial structure that "chaperones" survival of pathogens by by correcting misshapen proteins. The company uses its assay for internal drug discovery and validation of potential compounds.

It's unclear what DnaK inhibitors might be found by screening the 250,000 compounds in the NIH library, says Mike Sturgess, Chaperone's director of chemistry, but it's important to look at a varied data set. "From Chaperone's perspective, what we would like to see is a screen that has really covered a broad spectrum of chemical space," he says. "We have a lot of expertise in the peptide arena from the work that we've already done, and some of our work has taken us away from peptides toward small molecules, but they have a particular flavor."

Screening data will go into the NIH's PubChem database, says Carson Loomis, program director of the NIH's molecular library program. "The way it works," says Loomis, "is that they are working right along with the center that's doing the screening. So that's where they get access to the data, virtually as it's being generated." When data are reconfirmed, several weeks later, they are submitted to PubChem for public use.

That window, says Sturgess, gives Chaperone an opportunity to investigate potential new DnaK inhibitors. "I suspect that our internal discovery programs will probably be running in a parallel track to this," he says. Although Sturgess doesn't expect the screening to provide enough information for quick, meaningful patent applications, he foresees the possibility of finding broad and diverse DnaK inhibitors for further study.

Chaperone also benefits from the requirement to miniaturize its assaying protocols for HTS. "They run 384-well plate high-throughput screening," says Sturgess, but Chaperone's original protocol is for 96-well plates, so Chaperone may later market the HTS version to other companies as a tool.

The NIH established its screening network not as a drug development program but to draw government, business, and academia together for developing research tools to investigate small molecules. "We are really excited that we're having for-profit organizations applying to get access to this resource," says Loomis. "Chaperone is one of several biotech companies that have applied and is one of several that have had the quality of application and target importance to be accepted into screening by the network."

Chaperone also has U.S. Department of Defense funding for investigating treatments that act against engineered releases of potential bacterial bioterrorism agents like plague and tularemia, says Sturgess. "We have the possibility of doing something that is obviously going to be very useful to mankind." Like much of Chaperone's drug discovery work, the program looks at using DnaK inhibitors in combination with other antibiotics.