New bar coding system helps decode drug discovery

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

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 process of categorising the individual components of a chemical library from several months to only a few hours, said 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 said. ‘Using standard Raman or infrared spectrometers 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, Fenniri said.

Traditionally, drug candidates had to be synthesised and tested one at a time, a very time-consuming and labour-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 spectral imaging technology in the drug discovery process.

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 said.

‘This method relies on the use of specially designed ‘smart’ beads,’ he said. ‘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.’

Fenniri said the bar coded beads were intentionally synthesised 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 said.

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