Role of amino acid N-methylation in cyclosporins on ring opening and fragmentation mechanisms during collisionally induced dissociation in an ion trap

Journal of Mass Spectrometry : JMS
Marek KuzmaVladimír Havlícek

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.

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Citations

Jun 14, 2006·Journal of Mass Spectrometry : JMS·Alexandr JegorovVladimir Havlicek
Jul 12, 2002·Journal of Mass Spectrometry : JMS
Dec 24, 2008·Journal of Natural Products·Marek KuzmaVladimír Havlícek

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