Mechanistic studies of amide bond scission during acidolytic deprotection of Pip containing peptide.
Unusual TFA catalyzed cleavage reaction is reported for peptide containing pipecolic acid residues. Although the use of TFA under standard cleavage conditions is sufficiently mild to prevent degradation of the desired products, the amide bond between consecutive pipecolic acid residues is unexpectedly hydrolyzed by standard TFA treatment. The hydrolysis is proposed to proceed via an oxazolinium ion intermediate. This mechanism is supported by H/D exchange as observed by ESI-MS and NMR experiments.
Rubini
Chiara
C
Institute of Biomolecular Chemistry of CNR, Padua Unit, 35131 Padua, Italy.
Osler
Alessio
A
Calderan
Andrea
A
Guiotto
Andrea
A
Ruzza
Paolo
P
D000577:Amides / Q000737:chemistry*; D001665:Binding Sites; D002627:Chemistry, Physical; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D041961:Deuterium Exchange Measurement; D006868:Hydrolysis; D009682:Magnetic Resonance Spectroscopy / Q000379:methods / Q000592:standards; D008968:Molecular Conformation; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000302:isolation & purification; D010875:Pipecolic Acids / Q000737:chemistry*; D012015:Reference Standards; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods; D013237:Stereoisomerism; D014269:Trifluoroacetic Acid / Q000737:chemistry*
D000577:Amides; D010455:Peptides; D010875:Pipecolic Acids; D014269:Trifluoroacetic Acid; C031345:pipecolic acid