Peptomers: A versatile approach for the preparation of diverse combinatorial peptidomimetic bead libraries
Soren Ostergaard
Novo Research Institute, Novo Alle, DK-2880 Bagsvaerd, Denmark
Arne Holm
Research Center for Medical Biotechnology, Chemistry Department, Royal
Veterinary and Agricultural University, Thorvaldsensvej 40, DK-1871
Frederiksberg C, Denmark
Abstract
This report describes a versatile approach in the generation of
peptidomimetic bead libraries. The method is based on the preparation of
peptide-peptoid hybrids using the portioning-mixing procedure, which gives
diverse peptidomimetic bead libraries composed of peptides, peptoids and
peptide-peptoid hybrids. We term these peptomers, from
peptide-peptoid hybrid polymers. The synthesis of the
peptomers is easily accomplished by adapting the peptoid synthesis
strategy, in which a primary amine reacts with bromoacetic acid, and we
combine this methodology with conventional peptide synthesis. The sequence
of the active compound is deduced by conventional microsequencing using
Edman degradation chemistry, thus avoiding the synthesis of a coding
structure or the addition of molecular tags. We demonstrate the utility of
the peptomer approach by the synthesis of a bead library together with the
identification of novel peptidomimetic ligands binding to the
macromolecular targets streptavidin and the insulin receptor.
Keywords
coding, combinatorial peptidomimetic library, dual color assay, Edman
degradation, insulin receptor ligands, peptoid, streptavidin ligands
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