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New Technique Uses Imaging Technology To Speed Drug Discovery

Date:
January 29, 2001
Source:
Purdue University
Summary:
Scientists working to develop new pharmaceuticals will soon have a tool for sorting quickly through millions of compounds to identify the best drug candidates. Purdue University researchers have developed a method to sort and isolate chemical compounds as they are made, helping to easily identify the most biologically active compounds among millions of candidates.

WEST LAFAYETTE, Ind. — Scientists working to develop new pharmaceuticals will soon have a tool for sorting quickly through millions of compounds to identify the best drug candidates.

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Purdue University researchers have developed a method to sort and isolate chemical compounds as they are made, helping to easily identify the most biologically active compounds among millions of candidates.

The new method, which combines state-of-the-art imaging technology and combinatorial chemistry, is four to 12 times faster than current methods and promises to simplify and speed the drug discovery process.

"This method has several advantages over current methods and may be a boon for pharmaceutical industries that spend billions of dollars and thousands of man-hours working to develop new drugs," says Hicham Fenniri, assistant professor of chemistry, who directed the effort.

The new method relies on the use of specially designed "beads" that can be easily identified using standard spectroscopic techniques or multispectral imaging technology. Fenniri and his group developed the beads and then incorporated them into the screening process so that potential drug candidates can be sorted as they are developed.

"This is currently the fastest and most affordable method for screening chemical libraries in the search for new anti-viral, anti-cancer or anti-bacterial drugs," Fenniri says. "How much faster it works depends upon the method to which you compare it. For example, the fastest and closest method is at least four times slower at analyzing small groups of compounds and at least 10 times slower for large groups."

As a result, a 12-month screening process carried out using traditional techniques could be completed in less than one month for a large group of compounds, and less than three months for a small group, he says.

The technique, detailed in the Dec. 15 issue of the German scientific journal Angewandte Chemie, draws upon an area of research called combinatorial chemistry.

Combinatorial approaches have become popular in recent years because they provide an efficient way to create libraries with millions of chemical variants in a minimal number of chemical steps, Fenniri says. Using these methods, chemists can produce large collections of compounds of varied structure by sequentially linking different molecular building blocks.

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

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. Knowing the arrangement of individual building blocks for each compound could help in identifying those compounds that show the highest biological activity, Fenniri says.

His group has developed an alternative approach called "dual recursive deconvolution," or DRED, that dramatically simplifies the discovery of biologically active members from very large combinatorial libraries.

The method was developed by combining the features of a popular combinatorial method, called split synthesis, with new technology in multispectral imaging.

"Split synthesis is a combinatorial method that has proven to be especially efficient in generating large arrays of individual compounds," Fenniri says. "To help speed up the synthetic and screening processes, the compounds are generated on resin beads."

Fenniri and his group developed a series of new beads, called DRED beads. The beads have unique spectral features, allowing them to be easily identified using standard spectroscopic techniques or multispectral imaging technology. The latter method, developed at Purdue by chemistry Professor Dor Ben-Amotz, is an approach similar to infrared camera technology for night vision, which is able to generate images of objects that radiate heat or vibrations unique to their chemical composition.

The new method will allow researchers to identify unique members of a combinatorial library in as many steps as it takes to build the library itself.

"The identification of a particular combination out of a 64-million member library, for instance, would require only about 120 steps, without the need for sophisticated equipment or complicated and expensive screening procedures," Fenniri says. "This quick turnaround is possible because the beads can identify the type and location of various chemical building blocks in each compound."

The method also may hold potential for additional applications, such as the development of artificial receptors and catalysts.

The new process has been patented by Purdue, and the new DRED beads will soon become commercially available.


Story Source:

The above story is based on materials provided by Purdue University. Note: Materials may be edited for content and length.


Cite This Page:

Purdue University. "New Technique Uses Imaging Technology To Speed Drug Discovery." ScienceDaily. ScienceDaily, 29 January 2001. <www.sciencedaily.com/releases/2001/01/010129065848.htm>.
Purdue University. (2001, January 29). New Technique Uses Imaging Technology To Speed Drug Discovery. ScienceDaily. Retrieved March 29, 2015 from www.sciencedaily.com/releases/2001/01/010129065848.htm
Purdue University. "New Technique Uses Imaging Technology To Speed Drug Discovery." ScienceDaily. www.sciencedaily.com/releases/2001/01/010129065848.htm (accessed March 29, 2015).

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