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A 28 residue "retro" beta-peptide has been designed to self-assemble as a tetramer, successfully recapitulating the octameric beta-peptide bundle complex Zwit-1F. Z28, the largest beta-peptide synthesized to date, was achieved in a linear, microwave-assisted synthesis in 19% isolated yield and high purity. Z28 forms the expected tetrameric complex and is more stable and cooperative in its folding than Zwit-1F. The successful design and synthesis of Z28 is an important step toward true beta-amino acid proteins.

Toward β-Amino Acid Proteins: Design, Synthesis, and Characterization of a Fifteen Kilodalton β-Peptide Tetramer