Active esters for peptide bond formation are often too reactive resulting in unwanted side reactions. N-hydroxybenzotriazoles are widely used as additives for peptide bond formation in organic solvents. N-hydroxysuccinimide esters were found to be more suitable for applications in aqueous environments in terms of shelf life and stability, despite their limited reactivity. 

Ayman El-Faham, Fernando Albericio, Institute for Research in Biomedicine, Barcelona, Spain, and colleagues, tested a variety of N-alkyl-cyanoacetamido oximes (pictured) in order to find an optimal balance between reactivity and stability. In comparison to N-hydroxysuccinimide, all tested oximes performed better, while the configuration and coupling efficiency was retained. Two additives even showed a similar performance to known ethyl 2-cyano-2-(hydroxyimino)acetate (Oxyma).

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• Screening of N-Alkyl-Cyanoacetamido Oximes as Substitutes for N-Hydroxysuccinimide,
  Sherine N. Khattab, Ramon Subirós-Funosas, Ayman El-Faham, Fernando Albericio,
  ChemistryOpen 2012, 1(3), 147–152.
  DOI: 10.1002/open.201200012

ChemistryOpen – the first society-owned, open-access, chemistry journal – is a journal of ChemPubSoc Europe published by Wiley-VCH.