Enhancing molecular diversity of peptoid oligomers using amino acid synthons

Abstract

We report the use of unprotected amino acids as submonomer reagents in the solid-phase synthesis of N-substituted glycine peptoid oligomers. Subsequent coupling of an amine, alcohol, or thiol to the free carboxylate of the incorporated amino acid provides access to peptoids bearing amides, esters, and thioesters as side chain pendant groups and permits further elongation of the peptoid backbone. The palette of readily obtained building blocks suitable for solid-phase peptoid synthesis is substantially expanded through this protocol, further enhancing the chemical diversity and potential applications of sequence-specific peptoid oligomers.