The chemical synthesis of a highly hydrophobic membrane-associated peptide by native
chemical ligation (NCL) in an ionic liquid (IL) [C
2
mim][OAc]/buffer mixture
was achieved by employing peptide concentrations up to 11 mM. NCL was studied at
different pH and water content and compared to several “gold-standard”
ligation protocols. The optimized reaction protocol for the NCL in IL required the
addition of 40% water and pH adjustment to 7.0–7.5, resulting in ligation yields
of up to 80–95% within 1 to 4 h. This new ligation protocol is generally
applicable and outperforms current “gold-standard” NCL methods.
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