HBTU activation for automated Fmoc solid-phase peptide synthesis

Pept Res. 1991 Mar-Apr;4(2):95-101.


Excellent results have been obtained for the Fmoc solid-phase syntheses of peptides using the activating reagent 2-(1H-benzotriazol-1-yl)-1,1,3,3,-tetramethyluronium hexafluorophosphate (HBTU). Activation occurs very rapidly in N,N-dimethylformamide and N-methyl-pyrrolidone, optimal solvents for peptide-resin solvation. It has been observed that complete coupling reactions occur in only 10-30 min. Residues such as Arg, Ile, Leu and Val, which often require double coupling by other activation methods, react with high efficiency by single coupling when HBTU is used. The Fmoc/HBTU chemistry has recently been applied to the peptide synthesizers. The incorporation of trityl side-chain protection for Fmoc-Asn and Fmoc-Gln further enhances coupling efficiencies in difficult sequences.

MeSH terms

  • Amino Acid Sequence
  • Amino Acids / analysis
  • Automation
  • Fluorenes*
  • Kinetics
  • Molecular Sequence Data
  • Peptides / chemical synthesis*
  • Piperidines / analysis
  • Triazoles*
  • Urea / analogs & derivatives*


  • Amino Acids
  • Fluorenes
  • Peptides
  • Piperidines
  • Triazoles
  • piperidine
  • Urea
  • 2-(1H-benzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate