PEPTOMERS - A VERSATILE APPROACH FOR THE PREPARATION OF DIVERSE COMBINATORIAL PEPTIDOMIMETIC BEAD LIBRARIES

This report describes a versatile approach in the generation of peptid omimetic bead libraries. The method is based on the preparation of pep tide-peptoid hybrids using the portioning-mixing procedure, which give s diverse peptidomimetic bead libraries composed of peptides, peptoids and peptide-peptoid hybrids. We term these peptomers, from peptide-pe ptoid hybrid polymers. The synthesis of the peptomers is easily accomp lished by adapting the peptoid synthesis strategy, in which a primary amine reacts with bromoacetic acid, and we combine this methodology wi th conventional peptide synthesis. The sequence of the active compound is deduced by conventional microsequencing using Edman degradation ch emistry, thus avoiding the synthesis of a coding structure or the addi tion of molecular tags. We demonstrate the utility of the peptomer app roach by the synthesis of a bead library together with the identificat ion of novel peptidomimetic ligands binding to the macromolecular targ ets streptavidin and the insulin receptor.