Chemical synthesis of polar zipper peptides: motifs for potential protein association in inherited neurodegenerative diseases.

Syntheses of peptides containing contiguous repeats of glutamine or asparagine, related to sequences derived from proteins associated with neurodegenerative diseases, are described. Such homo-polymeric peptides are notoriously difficult to prepare due to the formation of aggregated structures during their solid phase synthesis. A novel approach using a randomized array of side chain protected and unprotected residues proved to be an effective strategy for preventing intermolecular peptide-chain association.