Synthesis of an O-acyl isopeptide by using native chemical ligation in an aqueous solvent system.

Abstract

O-Acyl isopeptides, in which the N-acyl linkage on the hydroxyamino acid residue (e.g. Ser and Thr) is replaced by an O-acyl linkage, generally suppress unfavorable aggregation properties derived from the corresponding parent peptides. Here, we report the synthesis of an O-acyl isopeptide of 34-mer pyroGlu-ADan (2), a component of amyloid deposits in hereditary familial Danish dementia, by using native chemical ligation. Native chemical ligation of pyroGlu(1) -ADan(1-21)-SCH2 CH2 SO3 (-) Na(+) (3) and Cys(22) -O-acyl isopeptide (4), in which the amino group of the Ser(29) residue at the isopeptide moiety was protected by an allyloxycarbonyl group, proceeded well in an aqueous solvent to yield a ligated O-acyl isopeptide (5). Subsequent disulfide bond formation and deprotection of the allyloxycarbonyl group followed by HPLC purification gave 2 with a reasonable overall yield. 2 was converted to the parent peptide 1 via an O-to-N acyl migration reaction. The sequential method, namely (i) native chemical ligation of the O-acyl isopeptide, (ii) HPLC purification as the O-acyl isopeptide form, and (iii) O-to-N acyl migration into the desired polypeptide, would be helpful to solve problems with HPLC purification of hydrophobic polypeptides in the process of chemical protein synthesis.

• Authors: Hiroyuki Kawashima, Tomomi Kuruma, Masayuki Yamashita, Youhei Sohma, Kenichi Akaji
• Journal: Journal of peptide science : an official publication of the European Peptide Society (J Pept Sci) Vol. 20 Issue 5 Pg. 361-5 (May 2014) ISSN: 1099-1387 [Electronic] England
• PMID: 24596115 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 European Peptide Society and John Wiley & Sons, Ltd.

Chemical References

• Oligopeptides
• Peptides
• Solvents
• Water

Topics

• Chromatography, High Pressure Liquid
• Hydrophobic and Hydrophilic Interactions
• Molecular Conformation
• Oligopeptides (chemical synthesis, chemistry, isolation & purification)
• Peptides (chemical synthesis, chemistry, isolation & purification)
• Solvents (chemistry)
• Water (chemistry)