'O-Acyl isopeptide method' for peptide synthesis: Solvent effects in the synthesis of Abeta1-42 isopeptide using 'O-acyl isodipeptide unit'

J Pept Sci. 2007 Dec;13(12):868-74. doi: 10.1002/psc.905.

Abstract

'O-Acyl isopeptide method' is an efficient synthetic method for peptides. We designed 'O-acyl isodipeptide units', Boc-Ser/Thr(Fmoc-Xaa)-OH, as important building blocks to enable routine use of the O-acyl isopeptide method. In the synthesis of an Abeta1-42 isopeptide using O-acyl isodipeptide unit Boc-Ser(Fmoc-Gly)-OH, a side reaction, resulting in the deletion of Ser(26) in the O-acyl isopeptide structure, was noticed during coupling of the unit. We observed that the side reaction occurred during the activation step and was solvent-dependent. In DMF or NMP, an intramolecular side reaction, originating from the activated species of the unit, occurred during the activation step. In non-polar solvents such as CHCl(3) or CH(2)Cl(2), the side reaction was less likely to occur. Using CH(2)Cl(2) as solvent in coupling the unit, the target Abeta1-42 isopeptide was synthesized with almost no major side reaction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyloid beta-Peptides / chemical synthesis*
  • Amyloid beta-Peptides / chemistry
  • Chloroform / chemistry*
  • Chromatography, High Pressure Liquid / methods
  • Dipeptides / chemical synthesis*
  • Dipeptides / chemistry
  • Magnetic Resonance Spectroscopy / methods
  • Mass Spectrometry / methods
  • Methylene Chloride / chemistry*
  • Molecular Conformation
  • Oligopeptides / chemical synthesis*
  • Oligopeptides / chemistry
  • Peptide Fragments / chemical synthesis*
  • Peptide Fragments / chemistry
  • Solvents / chemistry
  • Stereoisomerism

Substances

  • Amyloid beta-Peptides
  • Dipeptides
  • Oligopeptides
  • Peptide Fragments
  • Solvents
  • amyloid beta-protein (1-42)
  • Methylene Chloride
  • Chloroform