Synthetic Combinatorial Libraries: A New Tool for Drug Design
Development of new leads for drug design and structure/function relationship studies were revolutionized by the introduction of combinatorial or “library” techniques (for review see e.g. (Moos et al., 1993; Gallop et al., 1994; Gordon et al., 1994)). These techniques allow for the generation and screening of millions of potentially active structures. Due to the well developed and finely tuned synthetic methodology, peptides were the first group of compounds evaluated by this new approach. However, the next logical challenge is to synthesize libraries of nonpeptidic structures. The combinatorial library approach applied at Selectide consists of three basic steps: (i) chemical synthesis based on the split synthesis method yielding a library with one test compound structure per one bead; (ii) screening of the library either using an on-bead binding assay or a multiple step release assay; and (iii) recovery of positive beads and determination of the structure of the test compound (Lam et al., 1991).
KeywordsConformational Space Peptide Library Edman Degradation Diamino Acid Fractional Code
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