Département de chimie moléculaire

For more than a decade, the oxime ether ligation has proven to be one of the most efficient technique for the prepn. of various peptide conjugates. However, despite numerous reports, the prepn. of aminooxy-contg. 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 std. solid-phase peptide synthesis (SPPS) procedures for the prepn. of more complex aminooxy-peptides. The authors have studied the coupling of modified Fmoc-lysine contg. 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, the authors propose to protect the Aoa moiety with a 1-ethoxyethylidene group (Eei) to provide 2-(1-ethoxyethylideneaminooxy)acetic acid building block. The authors showed that the Eei group is fully compatible with std. 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 prepn. of aminooxy peptides. [on SciFinder(R)]