The aspartimide problem in Fmoc-based SPPS. Part II

J Pept Sci. 2003 Aug;9(8):518-26. doi: 10.1002/psc.473.

Abstract

The sequence dependence of base-catalysed aspartmide formation during Fmoc-based SPPS was systematically studied employing the peptide models H-Val-Lys-Asp-Xaa-Tyr-Ile-OH. The extent of formation of aspartimide and related by-products was determined by RP-HPLC. Considerable amounts of by-products were formed in the case of Xaa = Asp(OtBu), Arg(Pbf), Asn(Mtt), Cys(Acm) and unprotected Thr. Aspartimide formation could be diminished by incorporation of Asp(OMpe) or by employing milder methods for Fmoc cleavage, e.g. hexamethyleneimine/N-methylpyrrolidine/HOBt/NMP/DMSO 4:50:4:71:71 (v/v/w/v/v).

MeSH terms

  • Amino Acids / chemistry*
  • Aspartic Acid / analogs & derivatives*
  • Aspartic Acid / chemistry*
  • Bridged Bicyclo Compounds, Heterocyclic / chemistry
  • Chromatography, High Pressure Liquid
  • Fluorenes / chemistry*
  • Peptide Biosynthesis
  • Peptides / chemistry
  • Piperidines / chemistry

Substances

  • Amino Acids
  • Bridged Bicyclo Compounds, Heterocyclic
  • Fluorenes
  • N(alpha)-fluorenylmethyloxycarbonylamino acids
  • Peptides
  • Piperidines
  • Aspartic Acid
  • aspartimide
  • piperidine
  • 1,8-diazabicyclo(5.4.0)undec-7-ene