Role of amino acid N-methylation in cyclosporins on ring opening and fragmentation mechanisms during collisionally induced dissociation in an ion trap.
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.
Kuzma
Marek
M
Institute of Microbiology, Academy of Sciences of the Czech Republic, Vídenská 1083, CZ-142 20 Prague 4, Czech Republic.
Jegorov
Alexandr
A
Hesso
Antti
A
Tornaeus
Jarkko
J
Sedmera
Petr
P
Havlícek
Vladimír
V
D000596:Amino Acids / Q000737:chemistry*; D003524:Cyclosporins / Q000737:chemistry*; D005285:Fermentation; D008401:Gas Chromatography-Mass Spectrometry; D009682:Magnetic Resonance Spectroscopy; D008745:Methylation; D021241:Spectrometry, Mass, Electrospray Ionization; D009626:Terminology as Topic
D000596:Amino Acids; D003524:Cyclosporins