Abstract
The practical use of nonsupport-bound combinatorial libraries represents an important breakthrough in all the areas of basic research and drug discovery. The use of a wide variety of chemical transformations permits a range of peptidomimetic libraries to be generated that greatly expands the chemical diversity available. The results described in this chapter demonstrate that an existing peptide positional scanning- synthetic combinatorial libraries (PS-SCL) can be chemically transformed to generate a peptidomimetic SCL, from which highly active individual compounds can be identified. The synthesis and deconvolution methods developed for peptide libraries are easily applied to other types of chemical pharmacophores. The soluble nature of the nonsupport-bound combinatorial libraries is a distinct advantage over the other methods in that membrane-bound and whole cell assays can also be used. In addition, the deconvolution methods used allow the chemical structure of peptidic, peptidomimetic, and organic compounds to be determined based solely on the structural similarities of compounds, within each active pool or sublibrary.
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