1. Role of amino acidN-methylation in cyclosporins on ring opening and fragmentation mechanisms during collisionally induced dissociation in an ion trap
- Author
-
Petr Sedmera, Marek Kuzma, Antti Hesso, Jarkko Tornaeus, Alexandr Jegorov, and Vladimír Havlíček
- Subjects
Spectrometry, Mass, Electrospray Ionization ,Magnetic Resonance Spectroscopy ,Stereochemistry ,Chemistry ,Cyclosporins ,Protonation ,Mass spectrometry ,Methylation ,Gas Chromatography-Mass Spectrometry ,Dissociation (chemistry) ,Fragmentation (mass spectrometry) ,Terminology as Topic ,Cyclosporin a ,Fermentation ,Mass spectrum ,Ion trap ,Amino Acids ,Spectroscopy - Abstract
The product ion mass spectra (collisionally induced dissociation mass spectra) of 12 different cyclosporins modified at every N-methylated amino acid residue with respect to cyclosporin A were compared and the effect of N-demethylation on ring opening mechanisms was evaluated. The four preferential protonation sites were identified in [MeBmt(1)]-cyclosporins. Three sites represented the N-methylated nitrogens of Sar(3), MeLeu(6) and MeLeu(9), while the remaining one represented the lactone group formed by the intramolecular N,O-acyl shift. Selective N-demethylation resulted either in the deletion of the entire fragment ion series or its substantial attenuation. The structures of three new natural cyclosporins in the study were supported by NMR data.
- Published
- 2002
- Full Text
- View/download PDF