Synthesis of peptide amides by Fmoc-solid-phase peptide synthesis and acid labile anchor groups.
The preparation and use of new anchor groups for the synthesis of peptide amides by solid-phase peptide synthesis employing the Fmoc-method is described. Based on the structure of the 4,4'-dimethoxybenzhydryl group (Mbh) handles were developed, which could be cleaved by mild acid treatment to give carboxamides. The syntheses and application of Fmoc-amino-acid-(4-carboxylatomethyloxyphenyl-4'-methoxyphenyl) methyl amide and Fmoc-(4-carboxylatopropyloxyphenyl-4'-methoxyphenyl) methyl amide are described in detail. These handles were coupled to resins and a stepwise elongation of peptide chains proceeded smoothly with N alpha-9-fluorenylmethoxycarbonyl (Fmoc) amino acid derivatives using a carbodiimide/HOBt mediated reaction. The final cleavage of side-chain protecting groups and the release of the C-terminal amide moiety was achieved by the treatment with trifluoroacetic acid, dichloromethane in the presence of scavengers. Various peptides, such as the Leu-enkephalin amide and Leu-Gly-Gly-Gly-Gln-Gly-Lys-Val-Leu-Gly-NH2, which is a good substrate for F XIII, were prepared in high yields and purities.
Stüber
W
W
Research Laboratories of Behringwerke AG, Marburg, Federal Republic of Germany.
Knolle
J
J
Breipohl
G
G
D000577:Amides / Q000138:chemical synthesis*; D000596:Amino Acids / Q000138:chemical synthesis; D055598:Chemical Phenomena; D002621:Chemistry; D002625:Chemistry, Organic / Q000379:methods; D004743:Enkephalin, Leucine / Q000031:analogs & derivatives / Q000138:chemical synthesis; D005449:Fluorenes; D006863:Hydrogen-Ion Concentration; D010455:Peptides / Q000138:chemical synthesis*
D000577:Amides; D000596:Amino Acids; D005449:Fluorenes; C016456:N(alpha)-fluorenylmethyloxycarbonylamino acids; D010455:Peptides; D004743:Enkephalin, Leucine; C048614:enkephalinamide-Leu