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Updated: Jun 18, 2026
Solid Phase Synthesis of a Functionalized Bis-Peptide Using "Safety Catch" Methodology
Published on: May 15, 2012
On the use of N-dicyclopropylmethyl aspartyl-glycine synthone for backbone amide protection
René Röder1, Petra Henklein, Hardy Weisshoff
1Institute of Clinical and Molecular Virology, University of Erlangen-Nürnberg, D-91054 Erlangen, Germany.
Abstract:
To prevent aspartimide formation and related side products in Asp-Xaa, particularly Asp-Gly-containing peptides, usually the 2-hydroxy-4-methoxybenzyl (Hmb) backbone amide protection is applied for peptide synthesis according to the Fmoc-protocols. In the present study, the usefulness of the recently proposed acid-labile dicyclopropylmethyl (Dcpm) protectant was analyzed. Despite the significant steric hindrance of this bulky group, N-terminal H-(Dcpm)Gly-peptides are quantitatively acylated by potent acylating agents, and alternatively the dipeptide Fmoc-Asp(OtBu)-(Dcpm)Gly-OH derivative can be used as a building block. In contrast to the Hmb group, Dcpm is inert toward acylations, but is readily removed in the acid deprotection and resin-cleavage step.
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