Procedures for the Synthesis of Combinatorial Compounds

Compound collections and libraries generated by the combination of different chemical reactions and building blocks are valuable tools in the search for novel ligands. Such 

Recently, EVOTEC has developed a system for the homogeneous analysis of bead-surface interactions. This system will enable compound screening to take place without the need to remove compounds from the surface of the bead. The system also enables direct recovery of single beads for further analysis. By enabling the rapid, on-bead analysis of thousands of beads, the EVOTEC system eliminates a critical bottleneck, namely the need for deconvolution of solid-phase diversity. 

Solution-phase combinatorial chemistry overcomes the restrictions of solid-phase synthesis caused by the need to attach educts to, and release products from, the solid support. The adaptation of standard synthesis procedures to solid-phase chemistry is not necessary. On the other hand, the chemist must be careful to ensure that educts have reacted almost completely, and that excess reagents are removed after each reaction step this represents a challenge for automation and process control. A core molecule as a template with several reactive groups has been used to generate xanthenene [30] or piperazine [31] libraries, for example. An iterative process for identification can be carried out by the deletion of one of the building blocks. 

A hybrid between combinatorial synthesis on solid phase and in solution phase is the liquid-phase method characterized by the application of carrier polymers completely soluble in one solvent and insoluble in another solvent, for example functionalized polyethylene glycol [32,33]. 

Bioassays are influenced by protein-reactive compounds [34] and tolerate only limited numbers of non-related molecules. False-positive and false-negative results from screening of compound mixtures have been reported. For example, octa- and hexapeptide mixtures significantly depress binding of the hormone neuropeptide Y to its receptor when measured in a standard competition assay [35]. 

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