On-Resin Synthesis of Linear Aryl Thioether Containing Peptides and in-Solution Cyclization via Cysteine SNAr Reaction

Org Lett. 2022 Mar 4;24(8):1673-1677. doi: 10.1021/acs.orglett.2c00234. Epub 2022 Feb 23.

Abstract

Cyclic peptides represent one of the most promising therapeutic agents in drug discovery due to their good affinity and selectivity. Herein, an on-resin synthesis of aryl thioether containing peptides and a concise cyclization strategy via chemoselective cysteine SNAr reaction was developed. The arylation group could be incorporated into a series of amino acids and used for standard SPPS and peptides cyclization. Constructed cyclic peptides showed increased cellular uptakes compared to their linear peptides.

MeSH terms

  • Cyclization
  • Cysteine* / chemistry
  • Humans
  • Molecular Structure
  • Peptides / chemical synthesis
  • Peptides / chemistry
  • Peptides, Cyclic* / chemical synthesis
  • Peptides, Cyclic* / chemistry
  • Sulfides* / chemical synthesis
  • Sulfides* / chemistry

Substances

  • Cysteine
  • Sulfides
  • Peptides, Cyclic
  • Peptides