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Solid‐Phase Synthesis of the Aged‐Nonapeptide‐Nerve‐Agent Adduct of Butyrylcholinesterase as Reference Materials for Analytical Verification
Author(s) -
Bielmann Andreas,
Curty Christophe,
Bochet Christian G.
Publication year - 2017
Publication title -
helvetica chimica acta
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.74
H-Index - 82
eISSN - 1522-2675
pISSN - 0018-019X
DOI - 10.1002/hlca.201700198
Subject(s) - chemistry , adduct , moiety , butyrylcholinesterase , peptide , combinatorial chemistry , nerve agent , peptide synthesis , impurity , enzyme , organic chemistry , stereochemistry , biochemistry , acetylcholinesterase , aché
Two pathways were developed and investigated for the synthesis of the ‘aged’‐nonapeptide nerve‐agent bioadduct of human butyrylcholinesterase (BuChE). Considering the fast ageing of nerve‐agent adducts of BuChE in patients and biomedical samples this target molecule is of paramount relevance for quantitative analysis with respect to the Chemical Weapons Convention. Two approaches using a precursor bearing a hydroxyl on its phosphonyl moiety and a benzyl protected precursor were considered. Several impurities were identified and circumvented during the optimization of the peptide synthesis step. The ‘aged’‐nonapeptide adduct was successfully synthesized by solid‐phase‐peptide‐synthesis ( SPPS ).