Abstract
A method for the synthesis and screening of polymeric libraries for biologic activities in solution is described. Libraries are constructed on a completely random basis with one structure on one particle of solid support (bead). The screened structure is then released into solution in several distinct steps, allowing screening of aliquots of the library in the first step to identify a mixture containing a structure of interest. Biological evaluation of individual compounds released from the polymeric carrier is performed in the second step. Multiple release of equimolar amounts of the randomized compounds is achieved by use of a construct capable of intramolecular closure of the diketopiperazine ring under neutral conditions in the first stage release. The second release is accomplished by alkaline hydrolysis at higher pH or by ammonolysis by ammonia vapors.
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