N-to-C solid-phase peptide and peptide trifluoromethylketone synthesis using amino acid tert-butyl esters.
Solid-phase peptide synthesis in the N-to-C direction, opposite to the classical C-to-N direction of peptide synthesis, provides the synthetically versatile C-terminal carboxyl group for further modification into C-terminally modified peptide mimetics. These are of general interest as potential bioactive agents, particularly as protease inhibitors. Elaboration of peptide mimetics on the solid-phase would facilitate synthesis of peptide mimetic combinatorial libraries. This report describes an effective strategy for solid-phase inverse peptide synthesis based on readily available amino acid tert-butyl esters. The potential of this approach for peptide mimetic synthesis is demonstrated by the solid-phase synthesis of two peptide trifluoromethylketones.
Gutheil
William G
WG
Division of Pharmaceutical Sciences, School of Pharmacy, University of Missouri-Kansas City, 64110, USA. gutheilw@umkc.edu
Xu
Qingchai
Q
D000596:Amino Acids / Q000737:chemistry*; D002087:Butyrates / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid; D007202:Indicators and Reagents; D007659:Ketones / Q000138:chemical synthesis*; D019151:Peptide Library; D010455:Peptides / Q000138:chemical synthesis*; D013386:Succinates / Q000737:chemistry
D000596:Amino Acids; D002087:Butyrates; D007202:Indicators and Reagents; D007659:Ketones; D019151:Peptide Library; D010455:Peptides; D013386:Succinates