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Application of Affinity Selection/Mass Spectrometry to Determine the Structural Isomer of Parnafungins Responsible for Binding Polyadenosine Polymerase.

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Title: Application of Affinity Selection/Mass Spectrometry to Determine the Structural Isomer of Parnafungins Responsible for Binding Polyadenosine Polymerase.
Authors: Adam, Gregory C.1 gregory—adam@merck.com, Parish, Craig A.1, Wisniewski, Douglas1, Meng, Juncai1, Liu, Min1, Calati, Kathleen1, Stein, Benjamin D.1, Athanasopoulos, John1, Liberator, Paul1, Roemer, Terry1, Harris, Guy1, Chapman, Kevin T.1
Source: Journal of the American Chemical Society. 12/10/2008, Vol. 130 Issue 49, p16704-16710. 7p. 6 Graphs.
Subjects: Candida albicans, Spectrum analysis, Natural products, Stereoisomers, Pathogenic fungi, Antifungal agents
Abstract: To discover antifungal treatments that possess the desired characteristics of broad spectrum activity, a strong safety profile, and oral bioavailability, new discovery strategies must be implemented to identify structural classes of molecules capable of combating these microorganisms. One such technique that has been implemented is the Candida albicans Fitness Test, a whole cell screening platform capable of delineating the mechanism of action of compounds that demonstrate activity against the clinically relevant pathogenic fungus, C. albicans. Screening crude natural product extracts with this technology has resulted in the identification of a novel family of antifungal natural products, named the parnafungins, which inhibit the enzyme polyadenosine polymerase (PAP), a key component of the mRNA cleavage and polyadenylation complex. Owing to the rapid interconversion of the structural and stereoisomers of the parnafungins at neutral pH, the determination of the structural isomer with the highest affinity for PAP with standard biochemical assays has not been possible. Herein, we present an application of affinity-selection/mass spectrometry (AS-MS) to determine that the "straight" parnafungin structural isomer (parnafungin A) binds preferentially to PAP compared to the `bent" structural isomer (parnafungin B). [ABSTRACT FROM AUTHOR]
Copyright of Journal of the American Chemical Society is the property of American Chemical Society and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
Database: Engineering Source
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DbLabel: Engineering Source
An: 35760556
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PubType: Academic Journal
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  Data: Application of Affinity Selection/Mass Spectrometry to Determine the Structural Isomer of Parnafungins Responsible for Binding Polyadenosine Polymerase.
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  Data: <searchLink fieldCode="AR" term="%22Adam%2C+Gregory+C%2E%22">Adam, Gregory C.</searchLink><relatesTo>1</relatesTo><i> gregory—adam@merck.com</i><br /><searchLink fieldCode="AR" term="%22Parish%2C+Craig+A%2E%22">Parish, Craig A.</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Wisniewski%2C+Douglas%22">Wisniewski, Douglas</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Meng%2C+Juncai%22">Meng, Juncai</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Liu%2C+Min%22">Liu, Min</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Calati%2C+Kathleen%22">Calati, Kathleen</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Stein%2C+Benjamin+D%2E%22">Stein, Benjamin D.</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Athanasopoulos%2C+John%22">Athanasopoulos, John</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Liberator%2C+Paul%22">Liberator, Paul</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Roemer%2C+Terry%22">Roemer, Terry</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Harris%2C+Guy%22">Harris, Guy</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Chapman%2C+Kevin+T%2E%22">Chapman, Kevin T.</searchLink><relatesTo>1</relatesTo>
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  Data: <searchLink fieldCode="JN" term="%22Journal+of+the+American+Chemical+Society%22">Journal of the American Chemical Society</searchLink>. 12/10/2008, Vol. 130 Issue 49, p16704-16710. 7p. 6 Graphs.
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  Data: <searchLink fieldCode="DE" term="%22Candida+albicans%22">Candida albicans</searchLink><br /><searchLink fieldCode="DE" term="%22Spectrum+analysis%22">Spectrum analysis</searchLink><br /><searchLink fieldCode="DE" term="%22Natural+products%22">Natural products</searchLink><br /><searchLink fieldCode="DE" term="%22Stereoisomers%22">Stereoisomers</searchLink><br /><searchLink fieldCode="DE" term="%22Pathogenic+fungi%22">Pathogenic fungi</searchLink><br /><searchLink fieldCode="DE" term="%22Antifungal+agents%22">Antifungal agents</searchLink>
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  Data: To discover antifungal treatments that possess the desired characteristics of broad spectrum activity, a strong safety profile, and oral bioavailability, new discovery strategies must be implemented to identify structural classes of molecules capable of combating these microorganisms. One such technique that has been implemented is the Candida albicans Fitness Test, a whole cell screening platform capable of delineating the mechanism of action of compounds that demonstrate activity against the clinically relevant pathogenic fungus, C. albicans. Screening crude natural product extracts with this technology has resulted in the identification of a novel family of antifungal natural products, named the parnafungins, which inhibit the enzyme polyadenosine polymerase (PAP), a key component of the mRNA cleavage and polyadenylation complex. Owing to the rapid interconversion of the structural and stereoisomers of the parnafungins at neutral pH, the determination of the structural isomer with the highest affinity for PAP with standard biochemical assays has not been possible. Herein, we present an application of affinity-selection/mass spectrometry (AS-MS) to determine that the "straight" parnafungin structural isomer (parnafungin A) binds preferentially to PAP compared to the `bent" structural isomer (parnafungin B). [ABSTRACT FROM AUTHOR]
– Name: AbstractSuppliedCopyright
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  Data: <i>Copyright of Journal of the American Chemical Society is the property of American Chemical Society and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
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        Value: 10.1021/ja805531w
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      – Code: eng
        Text: English
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        PageCount: 7
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      – SubjectFull: Candida albicans
        Type: general
      – SubjectFull: Spectrum analysis
        Type: general
      – SubjectFull: Natural products
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      – SubjectFull: Stereoisomers
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      – SubjectFull: Pathogenic fungi
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      – SubjectFull: Antifungal agents
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      – TitleFull: Application of Affinity Selection/Mass Spectrometry to Determine the Structural Isomer of Parnafungins Responsible for Binding Polyadenosine Polymerase.
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              Text: 12/10/2008
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