Preparation of the very acid-sensitive Fmoc-Lys(Mtt)-OH. Application in the synthesis of side-chain to side-chain cyclic peptides and oligolysine cores suitable for the solid-phase assembly of MAPs and TASPs

Int J Pept Protein Res. 1995 May;45(5):488-96. doi: 10.1111/j.1399-3011.1995.tb01065.x.

Abstract

N alpha-9-Fluorenylmethoxycarbonyl-N epsilon-4=methyltrityl-lysine, [Fmoc-Lys(Mtt)-OH], was prepared in two steps from lysine, in 42% overall yield. The N epsilon-Mtt function can be quantitatively removed upon treatment with 1% TFA in dichloromethane or with a 1:2:7 mixture of acetic acid/trifluoroethanol/dichloromethane for 30 min and 1 h at room temperature, respectively. Under these conditions, groups of the tert-butyl type and peptide ester bonds to TFA-labile resins, such as the 2-chlorodiphenylmethyl- and the Wang-resin, remained intact. The utility of the new derivative in peptide synthesis has been exemplified with the synthesis of a cyclic cholecystokinin analog. As an example of further application, five types of lysine cores suitable for the solid-phase synthesis of one, two or three epitopes containing antigenic peptides or template-assembled synthetic proteins have been synthesized on Merrifield, Wang and 2-chlorodiphenylmethyl resin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Chromatography, High Pressure Liquid
  • Chromatography, Thin Layer
  • Epitopes / chemistry*
  • Fluorenes / chemistry*
  • Lysine / analogs & derivatives*
  • Lysine / chemical synthesis
  • Lysine / chemistry*
  • Molecular Sequence Data
  • Peptides, Cyclic / chemical synthesis*
  • Trityl Compounds / chemical synthesis*
  • Trityl Compounds / chemistry*

Substances

  • Epitopes
  • Fluorenes
  • N(alpha)-9-fluorenylmethoxycarbonyl-N(epsilon)-4-methyltrityllysine
  • Peptides, Cyclic
  • Trityl Compounds
  • Lysine