+ Site Statistics
References:
52,654,530
Abstracts:
29,560,856
PMIDs:
28,072,755
+ Search Articles
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ PDF Full Text
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn

+ Translate
+ Recently Requested

Application of affinity selection/mass spectrometry to determine the structural isomer of parnafungins responsible for binding polyadenosine polymerase



Application of affinity selection/mass spectrometry to determine the structural isomer of parnafungins responsible for binding polyadenosine polymerase



Journal of the American Chemical Society 130(49): 16704-16710



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).

(PDF emailed within 0-6 h: $19.90)

Accession: 051607946

Download citation: RISBibTeXText

PMID: 19049464

DOI: 10.1021/ja805531w



Related references

Affinity Selection-Mass Spectrometry Identifies a Novel Antibacterial RNA Polymerase Inhibitor. Acs Chemical Biology 12(5): 1346-1352, 2017

Application of affinity selection-mass spectrometry assays to purification and affinity-based screening of the chemokine receptor CXCR4. Combinatorial Chemistry & High Throughput Screening 15(6): 473-485, 2012

Energy resolved mass spectrometry of chlorogenic acids and its application to isomer quantification by direct infusion tandem mass spectrometry. Phytochemical Analysis, 2018

Application of thin-layer chromatography/infrared matrix-assisted laser desorption/ionization orthogonal time-of-flight mass spectrometry to structural analysis of bacteria-binding glycosphingolipids selected by affinity detection. Rapid Communications in Mass Spectrometry 24(7): 1032-1038, 2010

Identification of G-Quadruplex-Binding Inhibitors of Myc Expression through Affinity Selection-Mass Spectrometry. Slas Discovery 2472555218796656-2472555218796656, 2018

Identification of specific hdm2 binding peptides by affinity selection and mass spectrometry. FASEB Journal 11(9): A1427, 1997

Discovery of selective RNA-binding small molecules by affinity-selection mass spectrometry. Acs Chemical Biology: -, 2018

Application of combined high-performance thin-layer chromatography immunostaining and nanoelectrospray ionization quadrupole time-of-flight tandem mass spectrometry to the structural characterization of high- and low-affinity binding ligands of Shiga toxin 1. Rapid Communications in Mass Spectrometry 19(24): 3659-3665, 2005

Affinity selection-mass spectrometry and its emerging application to the high throughput screening of G protein-coupled receptors. Combinatorial Chemistry & High Throughput Screening 11(6): 427-438, 2008

Mass spectrometry--not just a structural tool: the use of guided ion beam tandem mass spectrometry to determine thermochemistry. Journal of the American Society for Mass Spectrometry 13(5): 419-434, 2002

Application of high-throughput affinity-selection mass spectrometry for screening of chemical compound libraries in lead discovery. Expert Opinion on Drug Discovery 2(2): 285-294, 2007

Kinase drug discovery by affinity selection/mass spectrometry (ASMS): application to DNA damage checkpoint kinase Chk1. Journal of Biomolecular Screening 11(7): 755-764, 2006

Structural isomer differentiation of 1,6-diaza-3,8-dioxabicyclo undecane and N,N-methylenebis by mass spectrometry. Rapid Communications in Mass Spectrometry 16(5): 447-452, 2002

Structural isomer differentiation of 1,6-diaza-3,8-dioxabicyclo[4.4.1]undecane and N,N'-methylenebis(oxazolidine) by mass spectrometry. Rapid Communications in Mass Spectrometry 16(5): 447-452, 2002

Structural isomer differentiation of 1,6-diaza-3,8-dioxabicyclo(4.4.1)undecane and N,N'-methylenebis(oxazolidine) by mass spectrometry. Rapid Communications in Mass Spectrometry 16(5): 447-452, 2002