Synthesis and application of acid labile anchor groups for the synthesis of peptide amides by Fmoc-solid-phase peptide synthesis.
The preparation and application of a new linker for the synthesis of peptide amides using a modified Fmoc-method is described. The new anchor group was developed based on our experience with 4,4'-dimethoxybenzhydryl (Mbh)-protecting group for amides. Lability towards acid treatment was increased dramatically and results in an easy cleavage procedure for the preparation of peptide amides. The synthesis of N-9-fluorenylmethoxycarbonyl- ([5-carboxylatoethyl-2.4-dimethoxyphenyl)- 4'-methoxyphenyl]-methylamin is reported in detail. This linker was coupled to a commercially available aminomethyl polystyrene resin. Peptide synthesis proceeded smoothly using HOOBt esters of Fmoc-amino acids. Release of the peptide amide and final cleavage of the side chain protecting groups was accomplished by treatment with trifluoroacetic acid-dichloromethane mixtures in the presence of scavengers. The synthesis of peptide amides such as LHRH and C-terminal hexapeptide of secretin are given as examples.
Breipohl
G
G
Research Laboratories of Hoechst AG, Frankfurt, Federal Republic of Germany.
Knolle
J
J
Stüber
W
W
D000577:Amides / Q000138:chemical synthesis*; D000595:Amino Acid Sequence; D000596:Amino Acids / Q000032:analysis*; D055598:Chemical Phenomena; D002621:Chemistry; D005449:Fluorenes; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis*; D013696:Temperature
D000577:Amides; D000596:Amino Acids; D005449:Fluorenes; C016456:N(alpha)-fluorenylmethyloxycarbonylamino acids; D010455:Peptides