Researchers at Affymax N.V. have devised a technology thatallows them to generate and screen large collections ofchemical compounds.
The technology, termed encoded synthetic libraries (ESL), isdescribed in a paper in the latest issue of The Proceedings ofthe National Academy of Sciences.
The ESL technology makes it possible to automate the synthesisand screening of billions of discrete chemical compounds on thesurface of microscopic, cell-size beads. It relies on the ability tosynthesize small amounts of those compounds on the beads one"building block" at a time. The scientists attach the firstbuilding block to the bead, and then attach to the same bead asnippet of DNA that acts as an identifying tag for that firstbuilding block.
Subsequent chemical building blocks are added one at a time,and for each there is a corresponding tag. Once built, thecandidate compounds are screened against a receptor ofinterest, labeled with a fluorophor, to check for possibleaffinities, explained Diana Kapp, manager of corporatecommunication and investor relations for Affymax(NASDAQ:AFMXF).
Any beads that contain compounds with high affinities for thetarget receptor can then be isolated by using a fluorescence-activated cell sorter. To actually get at that synthesizedcompound and determine its exact chemical composition, theresearchers turn to the DNA tags, which they use as a kind of"chemical bar code," Kapp explained. They amplify the DNAtags via PCR; because each tag is already "assigned" to aparticular synthetic building block, it's easy enough to deducethe structure of the candidate compound.
Affymax, through its wholly owned subsidiary AffymaxResearch Institute of Palo Alto, Calif., already has a receptorarsenal it is screening by its various technologies, includingESL, for promising drug leads, Kapp said.
The other technologies include recombinant peptide diversity,by which it's proven possible to generate billions of peptides onbacteriophage; and very large scale immobilized polymersynthesis (VLSIPS), an adaptation of semiconductor technologyfor creating compounds on the surface of a microchip.
Affymax's stock was up $1.25 a share on Monday, closing at$16.25.
-- Jennifer Van Brunt Senior Editor
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