Monitoring of peptide cyclization reactions by electrospray ionization mass spectrometry

Crude mixtures of difficult tetrapeptide cyclization reactions were analyzed by electrospray ionization mass spectrometry to optimize the production of cyclomonomer versus cyclodimer. The cationization phenomenon enabled the differentiation between monoprotonated and multiply charged ions of the same nominal mass as well as monoprotonated ions of aggregates and of cyclopolymers. Thus, a rapid and straightforward method was set up to assess without any product isolation and purification the nature of the synthesized compounds. Quantification of the various cyclic structures was then carried out by high performance liquid chromatography coupled to mass spectrometry.