Structural characterization of cyclosporin A, C and microbial bio-transformed cyclosporin A analog AM6 using HPLC–ESI–ion trap-mass spectrometry

Ahn, Eun Young; Shrestha, Anil; Hoang, Nguyen Huu; Hương, Nguyễn Lan; Yoon, Yeo Joon; Park, Je Won

doi:10.1016/j.talanta.2014.01.067

Cited by 8 publications

(9 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Nonetheless, valuable biological properties are drawing significant attention to study of cyclosporine A and its congeners, thus, fragmentation of this compound is relatively well studied. Numerous fragmentation patterns were established for CsA in the course of structural study of natural cyclosporins [16,30,31] and specific mass-spectrometric research devoted to unique side chain cleavage in MeBmt [32] and to the role of N-amino methylation in initial ring opening process [33]. Identification of isocyclosporin as one of the main hydrolysis products of cyclosporin A has drawn significant attention to differences in their mass-spectra, including MS/MS fragmentation [23,34].…”

Section: Fragmentation Of [M+2h] 2+ Ions Of Cyclosporinsmentioning

confidence: 99%

“…We analyzed distinguishable features in [M+2H] 2+ CID spectra of these compounds and attempted to attribute observed ions to known fragmentation mechanisms. We performed MS n experiments for key ions as previously described for [M+H] + ions [16] for better understanding of fragmentation of cyclosporins.…”

Section: Fragmentation Of [M+2h] 2+ Ions Of Cyclosporinsmentioning

confidence: 99%

“…Methods for analysis of cyclosporins in natural sources also draw significant attention. For example, the MS n analytical platform was worked out for CsA congener analysis, including biotransformed analogs [16]. Recently, the MS networking approach allowed to increase the diversity of peptidic natural products, including the chemical space of cyclosporins [17].…”

Section: Fig 1 Structures and Interconversions Of Cyclosporin A And Isocyclosporin Amentioning

confidence: 99%

See 2 more Smart Citations

Doubly Protonated Species Collision Induced Dissociation for Identification of Isocyclosporins

Baranova¹,

Chistov²,

Shuvalov³

et al. 2020

Preprint

View full text Add to dashboard Cite

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.

show abstract

Section: Fragmentation Of [M+2h] 2+ Ions Of Cyclosporinsmentioning

confidence: 99%

Section: Fragmentation Of [M+2h] 2+ Ions Of Cyclosporinsmentioning

confidence: 99%

Section: Fig 1 Structures and Interconversions Of Cyclosporin A And Isocyclosporin Amentioning

confidence: 99%

See 1 more Smart Citation

Doubly Protonated Species Collision Induced Dissociation for Identification of Isocyclosporins

Baranova¹,

Chistov²,

Shuvalov³

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…Cyclosporin A (CsA) is a cyclic nonribosomal 11-amino acid peptide produced by the fungus Tolypocladium inflatum, and is a widely used immunosuppressant [68]. CsA binds to the cytosolic protein cyclophilin in T-cells, and the CsA-cyclophilin complex inhibits calcineurin [69].…”

Section: Investigational Drugs Under Early Clinical Trialsmentioning

confidence: 99%

Investigational agents for treatment of traumatic brain injury

Xiong

Zhang

Mahmood

et al. 2015

Expert Opinion on Investigational Drugs

View full text Add to dashboard Cite

Introduction Traumatic brain injury (TBI) is a major cause of death and disability worldwide. To date, there are no pharmacologic agents proven to improve outcomes from TBI because all the Phase III clinical trials in TBI have failed. Thus, there is a compelling need to develop treatments for TBI. Areas covered The aim of this review is to provide an overview of select cell-based and pharmacological therapies under early development for the treatment of TBI, which seek to enhance cognitive and neurological functional recovery through neuroprotective and neurorestorative strategies. Expert’s opinion TBI elicits both complex degenerative and regenerative tissue responses in the brain. TBI can lead to cognitive, behavioral, and motor deficits. Although numerous promising neuroprotective treatment options have emerged from preclinical studies that mainly target the lesion, translation of preclinical effective neuroprotective drugs to clinical trials has proven challenging. Accumulating evidence indicates that the mammalian brain has a significant, albeit limited, capacity for both structural and functional plasticity as well as regeneration essential for spontaneous functional recovery after injury. A new therapeutic approach is to stimulate neurovascular remodeling by enhancing angiogenesis, neurogenesis, oligodendrogenesis, and axonal sprouting, which in concert, may improve neurological functional recovery after TBI.

show abstract

“…Cyclosporin A (CsA) is the most commonly used analog and was first isolated from soil fungus by multi-step extractions [7]. Reversed phase HPLC has been widely used to separate CsA and CsC [8] [9]. Due to structural similarity, separation of multiple Cyclosporin analogs was complicated and involved multiple chromatographic procedures.…”

Section: Introductionmentioning

confidence: 99%

Rapid Separation of Five Cyclosporin Analogs by Supercritical Fluid Chromatography

Shao¹,

Wang²,

Apedo³

et al. 2016

JASMI

View full text Add to dashboard Cite

Recently there has been a resurgence of interest in cyclic peptides due to their therapeutic advantages in terms of potency, permeability, proteolytic stability, and unique selectivity relative to traditional smaller drug molecules. Cyclosporin is a family of cyclic peptides widely used as autoimmune suppression agents. Cyclosporin analogs consist of eleven amino acids with the main difference lying at the side chain of its amino acid residues. In this study, a single step separation method was developed utilizing Supercritical Fluid Chromatography (SFC) to resolve five naturally occurring cyclosporin analogs (Cyclosporin A, B, C, D, and H) on a bare silica-packed column. The optimized method involved use of ethanol-modified carbon dioxide as mobile phase on a bare silica column at 80˚C and UV detection at 220 nm. Although column temperature and back pressure generally had insignificant effect on SFC separation, it was found in our study that increasing temperature and pressure greatly improved peak shape and resolution.

show abstract

Structural characterization of cyclosporin A, C and microbial bio-transformed cyclosporin A analog AM6 using HPLC–ESI–ion trap-mass spectrometry

Cited by 8 publications

References 26 publications

Doubly Protonated Species Collision Induced Dissociation for Identification of Isocyclosporins

Doubly Protonated Species Collision Induced Dissociation for Identification of Isocyclosporins

Investigational agents for treatment of traumatic brain injury

Rapid Separation of Five Cyclosporin Analogs by Supercritical Fluid Chromatography

Contact Info

Product

Resources

About