Evaluation of the final deprotection system for the solid-phase synthesis of Tyr(SO3H)-containing peptides with 9-fluorenylmethyloxycarbonyl (Fmoc)-strategy and its application to the synthesis of cholecystokinin (CCK)-12.
Acidolytic deprotection and cleavage conditions for an acid-labile Tyr(SO3H)-containing peptide were systematically examined with respect to acid, temperature, and scavenger. The 90% aqueous trifluoroacetic acid (TFA)-based reagent systems (90% aqueous TFA/m-cresol and 90% aqueous TFA/m-cresol/2-methylindole) at 4 degrees C were found to minimize the deterioration of Tyr(SO3Na) in the peptide. The latter deprotection/cleavage system was applied to the 9-fluorenylmethyloxycarbonyl (Fmoc)-based solid-phase synthesis of cholecystokinin (CCK)-12 on an acid-labile PAL-linked support (PAL = peptide amide linker), with Fmoc-Tyr(SO3Na)-OH as a building block.
Faculty of Pharmaceutical Sciences, University of Tokushima, Japan.
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Yagami
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Shiwa
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Futaki
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Kitagawa
D000595:Amino Acid Sequence; D002766:Cholecystokinin / Q000138:chemical synthesis*; D002851:Chromatography, High Pressure Liquid; D003408:Cresols; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis*; D014269:Trifluoroacetic Acid; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000737:chemistry
D003408:Cresols; D010455:Peptides; C005662:tyrosine O-sulfate; D014443:Tyrosine; D002766:Cholecystokinin; D014269:Trifluoroacetic Acid