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New bar coding system helps decode drug discovery

WEST LAFAYETTE, Ind. – Researchers sorting through large numbers of chemical compounds to identify new drug candidates may soon be heading for the express check-out lane.

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Purdue University chemists have developed a way to "bar code" individual chemical compounds, making it quick, easy and economical to identify the most biologically active ones among thousands of candidates in the drug-screening process.

The new method, which uses equipment that is readily available in most chemistry laboratories, will reduce the laborious process of categorizing the individual components of a chemical library from several months to only a few hours, says Hicham Fenniri, assistant professor of chemistry who directed the effort.

"The method works by assigning a unique bar coded bead to each compound as it is made," Fenniri says. "Using standard Raman or infrared spectrometers – equipment found in any conventional academic or industrial laboratory – the bar codes can be read, and the chemical nature of the active compounds instantaneously obtained."

What this means for researchers working to create "compound libraries" with millions of chemical variants is that time needed to identify active compounds is reduced to its bare minimum, or zero, Fenniri says.

In addition to drug discovery, the method may have applications in gene sequencing, biomedicine or biotechnology, he says. Several chemical companies are currently reviewing this technology, and the first generation of bar coded resins may reach the market within the next few months.

Details of the bar coding method were being presented at the American Chemical Society's national meeting in Chicago, which began Sunday and ends Thursday (8/26-30), and reported in a recent issue of the Journal of the American Chemical Society.

Traditionally, drug candidates had to be synthesized and tested one at a time, a very time-consuming and labor-intensive process. With the advent of combinatorial chemistry, pharmaceutical companies have been able to reduce the costs for drug development by several million dollars per drug candidate and reduce the time between the search for a drug to its clinical trials from an average of seven to less than two years.

In recent years, scientists have developed combinatorial methods to create compound libraries with millions of chemical variants in a minimal number of chemical steps. The compounds are generated on resin beads, porous plastic microspheres, by sequentially linking different molecular building blocks to them.

The problem is, as the libraries are assembled, the newly developed compounds are continually rearranged and resorted, making it difficult to track information about the order in which the building blocks are assembled.

Last year Fenniri's research group at Purdue developed a quick screening method called dual recursive deconvolution, or DRED, that, for the first time, incorporated state-of-the-art spectral imaging technology in the drug discovery process.

DRED was designed for use at the early stages in the drug discovery process where millions of compounds are screened for the identification of potential drug leads. The method cuts several months from the tedious process of categorizing the individual components of a chemical library.

The new bar coding strategy encompasses the early, as well as the advanced, stages of the drug discovery process where more focused libraries are designed to refine the leads from the early screening, Fenniri says.

"This method relies on the use of specially designed 'smart' beads," he says. "In addition to their role as support for chemical library synthesis, we designed them so that they would carry vital information about the chemistry to which they were subjected."

In other words, one can interrogate the beads at the end of the synthesis process to reveal the chemical nature of their cargo.

"Up until this new development, the beads had no role in library screening," Fenniri says. "This is a new paradigm in combinatorial chemistry, as the beads are no longer just compound carriers, but are, in addition, the repository of vital information about the chemical nature of these compounds."

Fenniri says the bar coded beads were intentionally synthesized with built-in spectroscopic bar codes. By incorporating infrared- and Raman-active groups that are chemically inert and readily identifiable with standard infrared or Raman spectrometers, each bead displays a unique vibrational spectrum that can be readily converted into a bar code for rapid identification.

The method simplifies the process of library deconvolution to a few simple steps: collecting the active beads, reading their bar code, assigning a chemical structure and confirming the result, he says.

"The bar codes do not deteriorate, even if the beads break down, since the spectroscopic information is evenly distributed over the entire bead," he says.

The method holds promise in a number of areas, including gene sequencing.

"One of the most exciting achievements in science over the past century is certainly the sequencing of the genome of humans and other organisms," he says. "In this post-genomic area, we are faced with the daunting task of decoding the properties and function of the hundreds of thousands of proteins encoded by DNA."

Combinatorial chemistry techniques, such as this, offer a viable strategy to establish a protein's function without knowing their chemical and structural identity, Fenniri says.

"Establishing their natural ligand specificity not only will expedite the identification of their physiological role, but will also provide the basis for the design of novel and potent pharmaceuticals," he says. "We envision that the bar coded resins will play a central role in proteomics as they currently provide the fastest and most affordable approach to screening large and small combinatorial libraries."

The method also may have applications in biomedicine and biotechnology.

"For example, it can be used to perform high throughput biological assays with thousands of antibodies, thereby maximizing the number of assays one can do at a time. It also could be used to search for specific sequences of DNA, such as in tests designed to identify viruses or toxins."

Source: Hicham Fenniri, (765) 494-5241,

Writer: Susan Gaidos, (765) 494-2081;

Purdue News Service: (765) 494-2096;

Purdue University researcher Hicham Fenniri (front to back), Laboratory for Chemical Nanotechnology director Alexander Ribbe and graduate student Yegor Zyrianov examine hyperspectral images and spectroscopic barcodes of newly designed resins. (Photo by Nick Judy, Purdue Marketing Communications.)

A publication-quality photograph is available at the News Service Web site and at the ftp site. Photo ID: Fenniri.barcode

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NOTE TO JOURNALISTS: Electronic or hard copies of the research paper about this work is available from Purdue News Service, (765) 494-2096,

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