Purdue University researchers have developed a method to sort and isolate chemical compounds as they are made. The new technique combines imaging technology and combinatorial chemistry and is said to be four to twelve times faster than current methods. The process also promises to simplify and speed up the drug discovery process.
The new method relies on the use of specially designed ‘beads’ that can be identified using standard spectroscopic techniques or multispectral imaging technology. Hicham Fenniri assistant professor of chemistry and director of the project helped developed the beads and then incorporated them into the screening process so 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,’ said Fenniri.
The technique draws upon an area of research called combinatorial chemistry.
Combinatorial approaches provide a way to create libraries with millions of chemical variants in a minimal number of chemical steps, Fenniri explained. Using these methods, chemists can produce large collections of compounds of varied structure by sequentially linking different molecular building blocks.
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 said.
His group has developed an alternative approach called ‘dual recursive deconvolution,’ or DRED, that simplifies the discovery of biologically active members from very large combinatorial libraries.
The method was developed by combining split synthesis with new technology in multispectral imaging.
Fenniri and his group developed a series of new beads, dubbed 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,’ said Fenniri. ‘This quick turnaround is possible because the beads can identify the type and location of various chemical building blocks in each compound.’