title: Solid-phase synthesis of diverse peptide tertiary amides by reductive amination.
abstract: The synthesis of libraries of conformationally constrained peptide-like oligomers is an important goal in combinatorial chemistry. In this regard an attractive building block is the N-alkylated peptide, also known as a peptide tertiary amide (PTA). PTAs are conformationally constrained because of allylic 1,3 strain interactions. We report here an improved synthesis of these species on solid supports through the use of reductive amination chemistry using amino acid-terminated, bead-displayed oligomers and diverse aldehydes. The utility of this chemistry is demonstrated by the synthesis of a library of 10,000 mixed peptoid-PTA oligomers.
authors.affiliation: Departments of Chemistry and Cancer Biology, The Scripps Research Institute , 130 Scripps Way, Jupiter, Florida 33458, United States.
authors.forename: Kevin
authors.initials: K
authors.lastname: Pels
authors.forename: Thomas
authors.initials: T
authors.lastname: Kodadek
mesh_terms: D000577:Amides / Q000138:chemical synthesis* / Q000737:chemistry; D000586:Amination; D008968:Molecular Conformation; D010084:Oxidation-Reduction; D010455:Peptides / Q000737:chemistry*; D060327:Solid-Phase Synthesis Techniques
chemical_list: D000577:Amides; D010455:Peptides
keywords: combinatorial chemistry; peptide; peptoid; reductive amination; solid-phase synthesis