Preparation of protected peptide amides using the Fmoc chemical protocol. Comparison of resins for solid phase synthesis.
Different resins were examined for their potential use in the solid phase synthesis of protected peptide amides using the 9-fluorenylmethoxycarbonyl (Fmoc) chemical protocol. The model protected peptide amide BocTyr-Gly-Gly-Phe-Leu-Arg(Pmc)NH2 (1) was synthesized on both the acid-labile 4-(2',4'-dimethoxyphenyl-Fmoc-aminomethyl)phenoxy resin (Rink amide resin) (2) and on resins containing the base-labile linker 4-hydroxymethylbenzoic acid. Of the resins examined only the methylbenzhydrylamine resin containing the 4-hydroxymethylbenzoic acid linkage, which was cleaved by ammonolysis in isopropanol, gave the model peptide 1 in good overall yield (53% including functionalization). Thus the synthesis of protected peptide amides by solid phase synthesis using Fmoc-protected amino acids with t-butyl-type side chain protecting groups is feasible. The choice of peptide-resin linkage and its cleavage conditions, however, are critical to the success of such syntheses. The potential application of this synthetic strategy to the preparation of novel peptide amides is discussed.
Story
S C
SC
College of Pharmacy, Oregon State University, Corvallis.
Aldrich
J V
JV
D000595:Amino Acid Sequence; D001559:Benzhydryl Compounds; D002851:Chromatography, High Pressure Liquid; D004399:Dynorphins / Q000737:chemistry; D005449:Fluorenes; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000737:chemistry; D012117:Resins, Synthetic; D016339:Spectrometry, Mass, Fast Atom Bombardment
C030545:4-methylbenzhydrylamine resin; D001559:Benzhydryl Compounds; D005449:Fluorenes; D009842:Oligopeptides; D012117:Resins, Synthetic; C075825:Rink amide resin; D004399:Dynorphins