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 and C, by Tolypocladium inflatum strains of marine origin (White Sea). Cyclosporins A–C contain an unusual amino acid, (4R)-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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Doubly Protonated Species Collision Induced Dissociation for Identification of Isocyclosporins

10.26434/chemrxiv.12919235 ◽

2020 ◽

Author(s):

Anna Baranova ◽

Alexey Chistov ◽

Maxim Shuvalov ◽

Anton Tyurin ◽

Mikhail Biryukov ◽

...

Keyword(s):

White Sea ◽

Immunosuppressive Drug ◽

Collision Induced Dissociation ◽

Tolypocladium Inflatum ◽

Time Production ◽

Ms Analysis ◽

Acidic Conditions ◽

Fragmentation Patterns ◽

First Time ◽

Unusual Amino Acid

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Profiling of Chlorogenic Acids from Bidens pilosa and Differentiation of Closely Related Positional Isomers with the Aid of UHPLC-QTOF-MS/MS-Based In-Source Collision-Induced Dissociation

Metabolites ◽

10.3390/metabo10050178 ◽

2020 ◽

Vol 10 (5) ◽

pp. 178 ◽

Cited By ~ 1

Author(s):

Anza-Tshilidzi Ramabulana ◽

Paul Steenkamp ◽

Ntakadzeni Madala ◽

Ian A. Dubery

Keyword(s):

Ion Trap ◽

Collision Induced Dissociation ◽

Stem Explants ◽

Positional Isomers ◽

Chlorogenic Acids ◽

Bidens Pilosa ◽

Geometrical Isomers ◽

Caffeoylquinic Acid ◽

Fragmentation Patterns ◽

First Time

Bidens pilosa is an edible herb from the Asteraceae family which is traditionally consumed as a leafy vegetable. B. pilosa has many bioactivities owing to its diverse phytochemicals, which include aliphatics, terpenoids, tannins, alkaloids, hydroxycinnamic acid (HCA) derivatives and other phenylpropanoids. The later include compounds such as chlorogenic acids (CGAs), which are produced as either regio- or geometrical isomers. To profile the CGA composition of B. pilosa, methanol extracts from tissues, callus and cell suspensions were utilized for liquid chromatography coupled to mass spectrometric detection (UHPLC-QTOF-MS/MS). An optimized in-source collision-induced dissociation (ISCID) method capable of discriminating between closely related HCA derivatives of quinic acids, based on MS-based fragmentation patterns, was applied. Careful control of collision energies resulted in fragment patterns similar to MS2 and MS3 fragmentation, obtainable by a typical ion trap MSn approach. For the first time, an ISCID approach was shown to efficiently discriminate between positional isomers of chlorogenic acids containing two different cinnamoyl moieties, such as a mixed di-ester of feruloyl-caffeoylquinic acid (m/z 529) and coumaroyl-caffeoylquinic acid (m/z 499). The results indicate that tissues and cell cultures of B. pilosa contained a combined total of 30 mono-, di-, and tri-substituted chlorogenic acids with positional isomers dominating the composition thereof. In addition, the tartaric acid esters, caftaric- and chicoric acids were also identified. Profiling revealed that these HCA derivatives were differentially distributed across tissues types and cell culture lines derived from leaf and stem explants.

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2,2-Bis(4-Hydroxyphenyl)-1-Propanol—A Persistent Product of Bisphenol A Bio-Oxidation in Fortified Environmental Water, as Identified by HPLC/UV/ESI-MS

Toxics ◽

10.3390/toxics9030049 ◽

2021 ◽

Vol 9 (3) ◽

pp. 49

Author(s):

Małgorzata Drzewiecka ◽

Monika Beszterda ◽

Magdalena Frańska ◽

Rafał Frański

Keyword(s):

Surface Water ◽

Bisphenol A ◽

Water Source ◽

Environmental Water ◽

Environmental Waters ◽

Esi Ms ◽

Ms Analysis ◽

Characteristic Fragmentation ◽

Fragmentation Patterns ◽

First Time

Biodegradation of bisphenol A in the environmental waters (lake, river, and sea) has been studied on the base of fortification of the samples taken and the biodegradation products have been analyzed using HPLC/UV/ESI-MS. Analysis of the characteristic fragmentation patterns of [M-H]− ions permitted unambiguous identification of the biodegradation products as 2,2-bis(4-hydroxyphenyl)-1-propanol or as p-hydroxyacetophenone, depending on the type of surface water source. The formation of 2,2-bis(4-hydroxyphenyl)-1-propanol was much more common than that of p-hydroxyacetophenone. Moreover, 2,2-Bis(4-hydroxyphenyl)-1-propanol has not been further biodegraded, in contrast to the p-hydroxyacetophenone, which was further mineralized. It has been proved, for the first time, that 2,2-bis(4-hydroxyphenyl)-1-propanol can be regarded as persistent product of bisphenol A biodegradation in the fortified environmental waters.

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Analysis of free and protein-bound nitrotyrosine in human plasma by a gas chromatography/mass spectrometry method that avoids nitration artifacts

Biochemical Journal ◽

10.1042/bj3450453 ◽

2000 ◽

Vol 345 (3) ◽

pp. 453-458 ◽

Cited By ~ 49

Author(s):

Matthew T. FROST ◽

Barry HALLIWELL ◽

Kevin P. MOORE

Keyword(s):

Reactive Nitrogen Species ◽

Plasma Proteins ◽

Biological Fluids ◽

Plasma Concentrations ◽

Normal Subjects ◽

Gas Chromatography Mass Spectrometry ◽

Highly Sensitive ◽

Acidic Conditions ◽

First Time

Measurement of nitrotyrosine in biological fluids and tissues is increasingly being used to monitor the production of reactive nitrogen species in vivo. The detection of nitrotyrosine in vivo has been reported with the use of a variety of methods including immunoassay, HPLC and GLC/MS. The validity of HPLC and immunoassays have been questioned with regard to their selectivity and sensitivity limits. In principle, the measurement of nitrotyrosine by GLC/MS permits a highly specific, highly sensitive and fully quantitative assay. The nitration of tyrosine under acidic conditions in the presence of nitrite is well documented. Derivatization for the full quantification of nitrotyrosine by using GLC/MS can lead to the artifactual nitration of tyrosine if performed under acidic conditions in the presence of nitrite. We describe a novel alkaline method for the hydrolysis and derivatization of nitrotyrosine and tyrosine, and demonstrate its applicability to the measurement of plasma concentrations of both free and protein-bound nitrotyrosine and tyrosine. A detection limit of 1 pg for nitrotyrosine and 100 pg for tyrosine has been achieved. Our method allows, for the first time, the analysis of free and protein-bound nitrotyrosine and tyrosine in biological samples. The plasma concentrations (means±S.E.M.) of free tyrosine and nitrotyrosine in eight normal subjects were 12±0.6 μg/ml and 14±0.7 ng/ml respectively. Plasma proteins contained tyrosine and nitrotyrosine at 60.7±1.7 μg/mg and 2.7±0.4 ng/mg respectively.

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Unique clinical spectrum with distinguishing diagnostic features in Vogt-Koyanagi-Harada syndrome

BMJ Case Reports ◽

10.1136/bcr-2019-231397 ◽

2019 ◽

Vol 12 (12) ◽

pp. e231397

Author(s):

Mamoona Sultan ◽

Adeena Khan ◽

Syed Shahid Habib ◽

Dheyab Abdulsalam

Keyword(s):

Nerve Conduction ◽

Immunosuppressive Drug ◽

Diagnostic Features ◽

Cutaneous Manifestations ◽

Ophthalmic Manifestations ◽

Systemic Corticosteroids ◽

Appropriate Treatment ◽

Ophthalmic Imaging ◽

First Time

A 36-year-old ulcerative colitis male patient on treatment for 7 years was referred to dermatology with resistant alopecia universalis and hypopigmented patches on limbs for 5 months. During this time he also reported to ophthalmology with acute bilateral decreased vision for 5 days. His examination revealed hyperaemic discs, multifocal retinal detachments and choroidal granulomas. Taking into account the revised diagnostic criteria, atypical course of disease in the form of early cutaneous presentation followed by ophthalmic manifestations was attributed to Vogt-Koyanagi-Harada syndrome (VKHS) which was supported by relevant investigations including ophthalmic imaging, MRI and nerve conduction studies. Subclinical nerve conduction abnormalities and white matter demyelination were also seen for the first time in a patient of VKHS. Appropriate treatment was required to prevent visual complications; therefore, systemic corticosteroids with steroid sparing immunosuppressive drug therapy showed significant improvement in vision on follow-up. Cutaneous manifestations were resilient to the entire regimen.

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New data on life cycles for three species of Fellodistomidae (Digenea) in the White Sea

Journal of Helminthology ◽

10.1017/s0022149x20000383 ◽

2020 ◽

Vol 94 ◽

Author(s):

D. Krupenko ◽

A. Uryadova ◽

A. Gonchar ◽

G. Kremnev ◽

V. Krapivin

Keyword(s):

Intermediate Host ◽

White Sea ◽

Taxonomic Status ◽

Life Cycles ◽

The White Sea ◽

Arctic Seas ◽

Buccinum Undatum ◽

The Family ◽

Second Intermediate Host ◽

First Time

Abstract Few digeneans of the family Fellodistomidae are known from the Russian Arctic seas. The taxonomic status of these species, their life cycles and host range raised recurrent questions, some of which remain unanswered. To revise the species composition and life cycles of fellodistomids in the White Sea, we searched for them in several known and suspected hosts: wolffish, flatfishes (definitive), gastropods of the family Buccinidae (second intermediate) and protobranch bivalves (first intermediate). Species identification was based both on morphology and 28S ribosomal RNA gene sequences. We found Fellodistomum agnotum in the White Sea for the first time. Buccinum undatum was proved to be intermediate host of both F. agnotum and Fellodistomum fellis, and metacercariae of F. fellis were registered from two more buccinid species: Buccinum scalariforme and Neptunea despecta. We also found metacercariae of F. agnotum and F. fellis producing eggs in the second intermediate host. Two fellodistomids were found in protobranch bivalves: sporocysts and cercariae of Steringophorus furciger in Nuculana pernula, and sporocysts with large furcocercous cercariae in Ennucula tenuis. The latter were identified as F. agnotum by molecular analysis; thus, the entire life cycle of this species was reconstructed.

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In Vitro Schistosomicidal Activity of the Alkaloid-Rich Fraction from Ruta graveolens L. (Rutaceae) and Its Characterization by UPLC-QTOF-MS

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2019/7909137 ◽

2019 ◽

Vol 2019 ◽

pp. 1-8 ◽

Cited By ~ 3

Author(s):

Lara Soares Aleixo de Carvalho ◽

Lucas Sales Queiroz ◽

Ismael José Alves Junior ◽

Ayla das Chagas Almeida ◽

Elaine Soares Coimbra ◽

...

Keyword(s):

Folk Medicine ◽

Peritoneal Macrophages ◽

Antileishmanial Activity ◽

Parasitic Infections ◽

Leishmania Braziliensis ◽

Ruta Graveolens ◽

Active Fraction ◽

Ms Analysis ◽

First Time

Schistosomiasis is a neglected tropical disease that affects million people worldwide, mostly in developing countries. Ruta graveolens (Rutaceae) is a plant used in folk medicine to treat several diseases, including parasitic infections. In this study, we reported the in vitro schistosomicidal activity of the R. graveolens extract (Rg) and its active fraction (Rg-FAE). Also, the characterization of Rg-FAE by UPLC-ESI-QTOF-MS analysis and its in vitro antileishmanial activity against Leishmania braziliensis were also performed. In vitro schistosomicidal assays were assessed against adult worms of S. mansoni, while cell viability against peritoneal macrophages was measured by MTT assay. Rg (100 μg/mL) exhibited noticeable schistosomicidal activity, causing 100% mortality and decreasing motor activity of all adult male and female schistosomes, but with low activity against L. braziliensis. After chromatographic fractionation of Rg, fraction Rg-FAE was obtained, showing high activity against adult schistosomes. UPLC-ESI-QTOF-MS analysis of Rg-FAE revealed the presence of eleven alkaloids and one furanocoumarin. No significant antileishmanial activity was found for Rg, while Rg-FAE exhibited activity against L. braziliensis promastigotes. We demonstrated, for the first time, that the R. graveolens extract (Rg) and its alkaloid-rich fraction (Rg-FAE) are active against adult worms of S. mansoni, with no significant cytotoxicity on macrophages. Our findings open the route to further antiparasitic studies with the active fraction of R. graveolens and its identified compounds, especially alkaloids.

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GC-MS Investigation of Amaryllidaceae Alkaloids in Galanthus xvalentinei nothosubsp. subplicatus

Natural Product Communications ◽

10.1177/1934578x1300800312 ◽

2013 ◽

Vol 8 (3) ◽

pp. 1934578X1300800

Author(s):

Buket Bozkurt Sarikaya ◽

Strahil Berkov ◽

Jaume Bastida ◽

Gulen Irem Kaya ◽

Mustafa Ali Onur ◽

...

Keyword(s):

Inhibitory Activity ◽

Anticholinesterase Activity ◽

Amaryllidaceae Alkaloids ◽

Acetylcholinesterase Inhibitory Activity ◽

Aerial Parts ◽

Ms Analysis ◽

Ellman’S Method ◽

First Time

A GC-MS analysis of alkaloids in the aerial parts and bulbs of Galanthus x valentinei nothosubsp. subplicatus was performed for the first time. Totally, twenty-six alkaloids were identified, of which tazettine and galanthindole were the major ones. Acetylcholinesterase inhibitory activity of the alkaloidal extracts was determined using modified in vitro Ellman's method. Significant anticholinesterase activity was observed in the tested samples (bulbs: IC50 = 21.3 μg/mL, aerial parts: IC50 = 16.3 μg/mL).

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Study of forced degradation behaviour of cobicistat and atazanavir using LC/ESI/QTOF/MS; a combination of in-sourced and collision-induced dissociation for evaluation of the fragmentation patterns of degradation products

New Journal of Chemistry ◽

10.1039/c8nj03418d ◽

2018 ◽

Vol 42 (23) ◽

pp. 19113-19128

Author(s):

Shandilya Mahamuni Baira ◽

Padmini Gunupudi ◽

Vigjna Abbaraju ◽

Srinivas R. ◽

M. V. N. Kumar Talluri

Keyword(s):

Degradation Products ◽

Collision Induced Dissociation ◽

Forced Degradation ◽

Degradation Behaviour ◽

Fragmentation Patterns

The present study describes the LC/MS/MS characterization of degradation products of cobicistat and atazanavir.

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Chemical Investigations of Essential Oils from Endemic Cupressaceae Trees from New Caledonia

Natural Product Communications ◽

10.1177/1934578x1000500630 ◽

2010 ◽

Vol 5 (6) ◽

pp. 1934578X1000500

Author(s):

Nicolas Lebouvier ◽

Chantal Menut ◽

Edouard Hnawia ◽

Audrey Illinger ◽

Pierre Cabalion ◽

...

Keyword(s):

Essential Oils ◽

New Caledonia ◽

Volatile Components ◽

Ms Analysis ◽

Leaf Oil ◽

High Level ◽

First Time

The volatile components obtained by hydrodistillation of leaves of C. neocaledonica Dummer, C. sulcata (Parlatore) Schlechter and N. pancheri (Carrière) de Laubenfels from New Caledonia were investigated for the first time by a combination of GC and GC–MS analysis, and compared with the heartwood oil compositions of the three species. The essential oils from C. sulcata and C. neocaledonica leaves contain a majority of monoterpenes while the leaf oil of N. pancheri is characterized by a high level of sesquiterpenoids. On the basis of the sesquiterpenoid composition of the wood- and leaf oils, N. pancheri is closely related to both New Caledonian Callitris spp. However, C. sulcata and C. neocaledonica oils remain distinct from N. pancheri and the Australian Callitris oils by the presence of compounds biosynthetically related to the bisabolyl cation, mainly barbatenes and thujopsene.

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