title: 1-Ethoxyethylidene, a new group for the stepwise SPPS of aminooxyacetic acid containing peptides.
abstract: For more than a decade, the oxime ether ligation has proven to be one of the most efficient technique for the preparation of various peptide conjugates. However, despite numerous reports, the preparation of aminooxy-containing peptides is still hampered by N-overacylation of the NH-O function either during its incorporation or through the peptide-chain elongation. This restricts the introduction of protected-NH-O function at the last acylation step and prevents the use of standard solid-phase peptide synthesis (SPPS) procedures for the preparation of more complex aminooxy-peptides. We have studied the coupling of modified Fmoc-lysine containing either N-Boc- or N,N'-bis-Boc-protected aminooxyacetic acids (Aoa) during the elongation of the peptide chain and found that none of them is adequate. To circumvent this limitation, we propose to protect the Aoa moiety with a 1-ethoxyethylidene group (Eei) to provide 2-(1-ethoxyethylideneaminooxy)acetic acid building block. We showed that the Eei group is fully compatible with standard SPPS conditions and safely allows the multiple incorporation of the aminooxy functionality into the growing peptide. Since Eei-protected Aoa remains as flexible as normal amino acids in peptide synthesis, it may become the rule for the straightforward preparation of aminooxy peptides.
authors.affiliation: DCM UMR CNRS 5250 & ICMG-FR2607, Université Joseph Fourier, BP 53, 38041, Grenoble cedex 9, France.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Foillard
authors.forename: Martin Ohsten
authors.initials: MO
authors.lastname: Rasmussen
authors.forename: Jesus
authors.initials: J
authors.lastname: Razkin
authors.forename: Didier
authors.initials: D
authors.lastname: Boturyn
authors.forename: Pascal
authors.initials: P
authors.lastname: Dumy
mesh_terms: D000625:Aminooxyacetic Acid / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid; D005019:Ethyl Ethers / Q000737:chemistry*; D007700:Kinetics; D015394:Molecular Structure; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry*
chemical_list: D005019:Ethyl Ethers; D010455:Peptides; D000625:Aminooxyacetic Acid