'O-Acyl isopeptide method' for peptide synthesis: Solvent effects in the synthesis of Abeta1-42 isopeptide using 'O-acyl isodipeptide unit'.
'O-Acyl isopeptide method' is an efficient synthetic method for peptides. We designed 'O-acyl isodipeptide units', Boc-Ser/Thr(Fmoc-Xaa)-OH, as important building blocks to enable routine use of the O-acyl isopeptide method. In the synthesis of an Abeta1-42 isopeptide using O-acyl isodipeptide unit Boc-Ser(Fmoc-Gly)-OH, a side reaction, resulting in the deletion of Ser(26) in the O-acyl isopeptide structure, was noticed during coupling of the unit. We observed that the side reaction occurred during the activation step and was solvent-dependent. In DMF or NMP, an intramolecular side reaction, originating from the activated species of the unit, occurred during the activation step. In non-polar solvents such as CHCl(3) or CH(2)Cl(2), the side reaction was less likely to occur. Using CH(2)Cl(2) as solvent in coupling the unit, the target Abeta1-42 isopeptide was synthesized with almost no major side reaction.
Taniguchi
Atsuhiko
A
Department of Medicinal Chemistry, Center for Frontier Research in Medicinal Science, 21st Century COE Program, Kyoto Pharmaceutical University, Yamashina-ku, Kyoto 607-8412, Japan.
Yoshiya
Taku
T
Abe
Naoko
N
Fukao
Fukue
F
Sohma
Youhei
Y
Kimura
Tooru
T
Hayashi
Yoshio
Y
Kiso
Yoshiaki
Y
D016229:Amyloid beta-Peptides / Q000138:chemical synthesis* / Q000737:chemistry; D002725:Chloroform / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004151:Dipeptides / Q000138:chemical synthesis* / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D013058:Mass Spectrometry / Q000379:methods; D008752:Methylene Chloride / Q000737:chemistry*; D008968:Molecular Conformation; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000737:chemistry; D010446:Peptide Fragments / Q000138:chemical synthesis* / Q000737:chemistry; D012997:Solvents / Q000737:chemistry; D013237:Stereoisomerism