title: Solid-phase synthesis of functionalized bis-peptides.
abstract: We demonstrate the first solid-phase synthesis of highly functionalized bis-peptides. Bis-peptides are ladder oligomers composed of stereochemically pure, cyclic bis-amino acids joined by substituted diketopiperazine linkages. They have a shape-programmable backbone that is controlled by controlling the stereochemistry and sequence of the monomers within each oligomer. Functionalized bis-peptides are assembled using a new amide bond forming reaction (acyl-transfer coupling) that we have previously developed and a novel activation strategy that allows the sequential formation of penta- and hexa-substituted diketopiperazines from extremely hindered N-alkyl-alpha,alpha-disubstituted amino acids. We present mechanistic evidence that acyl-transfer coupling is competitive with direct acylation in the formation of hindered amide bonds. We also detail the synthesis of four functionalized bis-peptides, and that by combining bis-peptides with amino acids through diketopiperazine linkages, bis-peptides can mimic the display of residues i, i+4, i+7 of an alpha-helical peptide.
authors.affiliation: Department of Chemistry, University of Pittsburgh, Pittsburgh, PA 15213, USA.
authors.forename: Zachary Z
authors.initials: ZZ
authors.lastname: Brown
authors.forename: Jennifer
authors.initials: J
authors.lastname: Alleva
authors.forename: Christian E
authors.initials: CE
authors.lastname: Schafmeister
mesh_terms: D000215:Acylation; D000596:Amino Acids / Q000138:chemical synthesis* / Q000737:chemistry; D003998:Dicarboxylic Acids / Q000138:chemical synthesis / Q000737:chemistry; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry; D057786:Peptidomimetics; D060327:Solid-Phase Synthesis Techniques
chemical_list: D000596:Amino Acids; D003998:Dicarboxylic Acids; D010455:Peptides; D057786:Peptidomimetics