Doubly Protonated Species Collision Induced Dissociation for Identification of Isocyclosporins

Nonribosomal cyclopeptide cyclosporin A (CsA), produced by fungus Tolypocladium inflatum , is an extremely important immunosuppressive drug used in organ transplantations and for therapy of autoimmune diseases. Here we report for the first time production of CsA, along with related cyclosporins B an...

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Bibliographic Details
Main Authors: Baranova, Anna, Chistov, Alexey, Shuvalov, Maxim, Tyurin, Anton, Biryukov, Mikhail, Ivanov, Igor, Sadykova, Vera, Kurakov, Aleksander, Sregeeva, Albina, Korshun, Vladimir, Alferova, Vera
Format: Other/Unknown Material
Language:unknown
Published: American Chemical Society (ACS) 2020
Subjects:
White Sea
Online Access:http://dx.doi.org/10.26434/chemrxiv.12919235
https://ndownloader.figshare.com/files/24578759
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Summary:Nonribosomal cyclopeptide cyclosporin A (CsA), produced by fungus Tolypocladium inflatum , is an extremely important immunosuppressive drug used in organ transplantations and for therapy of autoimmune diseases. Here we report for the first time production of CsA, along with related cyclosporins B and C, by Tolypocladium inflatum strains of marine origin (White Sea). Cyclosporins A–C contain an unusual amino acid, (4 R )-4-(( E )-2-butenyl)-4, N -dimethyl-l-threonine (MeBmt), and are prone to isomerization to non-active isocyclosporine by N→O acyl shift of valine connected to MeBmt in acidic conditions. CsA and isoCsA are not distinguishable in MS analysis of [M+H] + ions due to the rapid [CsA+H] + →[isoCsA+H] + conversion. We found that the N→O acyl shift is completely suppressed in cyclosporine [M+2H] 2+ ions, and their MS/MS fragmentation can be used for rapid and unambiguous analysis of cyclosporins and isocylosporins. The fragmentation patterns of [CyA+2H] 2+ and [isoCyA+2H] 2+ ions were analyzed and explained. The developed approach could be useful for MS analysis of other peptides containing β-hydroxy-α-amino acids.

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