Synthesis of peptide amides using Fmoc-based solid-phase procedures on 4-methylbenzhydrylamine resins.
A two-step low-high protocol for the efficient synthesis of peptide amides is described. The protocol exploits the efficiency of Reagent K for side-chain deprotection with the capability of the hard acid trifluoromethane-sulfonic acid (TFSMA) for cleavage of the peptide from the benzhydrylamine resin. This procedure has proven to be an effective method for the synthesis of peptide amides. The formation of alpha-aminosuccinimide (Asu) derivatives were observed with aspartyl-containing peptides as a minor side reaction product of this procedure, but this Asp-->Asu rearrangement could be successfully suppressed by employing low temperature conditions. The N- to O-acyl rearrangement of threonine and/or serine residues also only occurred to a minor extent under these synthetic conditions.
Thompson
P E
PE
Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria, Australia.
Keah
H H
HH
Gomme
P T
PT
Stanton
P G
PG
Hearn
M T
MT
D000577:Amides / Q000138:chemical synthesis / Q000737:chemistry; D000595:Amino Acid Sequence; D001559:Benzhydryl Compounds / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid; D008698:Mesylates / Q000737:chemistry; D008969:Molecular Sequence Data; D010446:Peptide Fragments; D010455:Peptides / Q000138:chemical synthesis*; D012694:Serine / Q000737:chemistry / Q000378:metabolism; D013912:Threonine / Q000737:chemistry / Q000378:metabolism
D000577:Amides; D001559:Benzhydryl Compounds; D008698:Mesylates; D010446:Peptide Fragments; D010455:Peptides; D013912:Threonine; D012694:Serine; C070954:4-methylbenzhydrylamine; C012077:trifluoromethanesulfonic acid