Solid-phase synthesis of tailed cyclic peptides: The use of α-allyl-protected aspartic acid leads to aspartimide and tetramethylguanidinium formation
✍ Scribed by Dominique Delforge; Marc Dieu; Edouard Delaive; Muriel Art; Barbara Gillon; Bart Devreese; Martine Raes; Jozef Beeumen; José Remacle
- Publisher
- Springer Netherlands
- Year
- 1996
- Tongue
- English
- Weight
- 651 KB
- Volume
- 3
- Category
- Article
- ISSN
- 1573-3149
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✦ Synopsis
This paper discusses the application of a method developed for cyclic peptide synthesis using allyl-based sidechain-protecting groups to obtain a so-called tailed cyclic peptide, a cyclic peptide bearing a side-chain anchoring tail. The method used for the synthesis ofcyclo[-D-Val-Arg-Gly-Asp-Asp(-eAhx-Cys-NH2)-] incorporates the c~-allylprotected aspartic acid Fmoc-L-Asp-OA1. A major side reaction, resulting in aspartimide formation, was observed when Fmoc-L-Asp-OA1 was incorporated into the sequence at the N-terminus of 6-aminohexanoic acid (eAhx). This side reaction leads to an aspartimidyl linear peptide with the same molecular weight as the expected cyclized peptide. Additionally, the undesired peptide contains a free amino terminus, which was responsible for further side reactions during the subsequent steps of the synthesis, mainly tetramethylguanidinium formation (M + 98) in TBTUinduced cyclization, and acetylation (M +42).