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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American Chemical Society (ACS)
2020
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cracsoc:10.26434/chemrxiv.12919235.v1 2024-04-07T07:56:25+00:00 Doubly Protonated Species Collision Induced Dissociation for Identification of Isocyclosporins Baranova, Anna Chistov, Alexey Shuvalov, Maxim Tyurin, Anton Biryukov, Mikhail Ivanov, Igor Sadykova, Vera Kurakov, Aleksander Sregeeva, Albina Korshun, Vladimir Alferova, Vera 2020 http://dx.doi.org/10.26434/chemrxiv.12919235.v1 https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c74f890f50db631e397414/original/doubly-protonated-species-collision-induced-dissociation-for-identification-of-isocyclosporins.pdf unknown American Chemical Society (ACS) https://creativecommons.org/licenses/by-nc-nd/4.0/ posted-content 2020 cracsoc https://doi.org/10.26434/chemrxiv.12919235.v1 2024-03-08T00:16:26Z 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. Other/Unknown Material White Sea ACS Publications White Sea |
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ACS Publications |
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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. |
format |
Other/Unknown Material |
author |
Baranova, Anna Chistov, Alexey Shuvalov, Maxim Tyurin, Anton Biryukov, Mikhail Ivanov, Igor Sadykova, Vera Kurakov, Aleksander Sregeeva, Albina Korshun, Vladimir Alferova, Vera |
spellingShingle |
Baranova, Anna Chistov, Alexey Shuvalov, Maxim Tyurin, Anton Biryukov, Mikhail Ivanov, Igor Sadykova, Vera Kurakov, Aleksander Sregeeva, Albina Korshun, Vladimir Alferova, Vera Doubly Protonated Species Collision Induced Dissociation for Identification of Isocyclosporins |
author_facet |
Baranova, Anna Chistov, Alexey Shuvalov, Maxim Tyurin, Anton Biryukov, Mikhail Ivanov, Igor Sadykova, Vera Kurakov, Aleksander Sregeeva, Albina Korshun, Vladimir Alferova, Vera |
author_sort |
Baranova, Anna |
title |
Doubly Protonated Species Collision Induced Dissociation for Identification of Isocyclosporins |
title_short |
Doubly Protonated Species Collision Induced Dissociation for Identification of Isocyclosporins |
title_full |
Doubly Protonated Species Collision Induced Dissociation for Identification of Isocyclosporins |
title_fullStr |
Doubly Protonated Species Collision Induced Dissociation for Identification of Isocyclosporins |
title_full_unstemmed |
Doubly Protonated Species Collision Induced Dissociation for Identification of Isocyclosporins |
title_sort |
doubly protonated species collision induced dissociation for identification of isocyclosporins |
publisher |
American Chemical Society (ACS) |
publishDate |
2020 |
url |
http://dx.doi.org/10.26434/chemrxiv.12919235.v1 https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c74f890f50db631e397414/original/doubly-protonated-species-collision-induced-dissociation-for-identification-of-isocyclosporins.pdf |
geographic |
White Sea |
geographic_facet |
White Sea |
genre |
White Sea |
genre_facet |
White Sea |
op_rights |
https://creativecommons.org/licenses/by-nc-nd/4.0/ |
op_doi |
https://doi.org/10.26434/chemrxiv.12919235.v1 |
_version_ |
1795674296641650688 |