Abstract
This report describes a versatile approach in thegeneration of peptidomimetic bead libraries. Themethod is based on the preparation of peptide–peptoidhybrids using the portioning–mixing procedure, whichgives diverse peptidomimetic bead libraries composedof peptides, peptoids and peptide–peptoid hybrids. Weterm these peptomers, from peptide–peptoidhybrid polymers. The synthesis of the peptomersis easily accomplished by adapting the peptoidsynthesis strategy, in which a primary amine reactswith bromoacetic acid, and we combine this methodologywith conventional peptide synthesis. The sequence ofthe active compound is deduced by conventionalmicrosequencing using Edman degradation chemistry,thus avoiding the synthesis of a coding structure orthe addition of molecular tags. We demonstrate theutility of the peptomer approach by the synthesis ofa bead library together with the identification ofnovel peptidomimetic ligands binding to themacromolecular targets streptavidin and the insulin receptor.