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

Adam, Gregory C.; Parish, Craig A.; Wisniewski, Douglas; Meng, Juncai; Liu, Min; Calati, Kathleen; Stein, Benjamin D.; Athanasopoulos, John; Liberator, Paul; Roemer, Terry; Harris, Guy H.; Chapman, Kevin T.

doi:10.1021/ja805531w

Cited by 25 publications

(19 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Applications of SEC AS‐MS to cancer drug discovery have included screening for ligands to cyclin dependent 2 and its cyclin A subunit, 47 screening 15 Nf‐κB pathway proteins for anti‐inflammation compounds, 50 and in an example of a target not amenable to conventional HTS and screening for inhibitors of the Myc oncogene that bind to the G‐quadruplex, a G‐rich DNA secondary structure found within the Myc promoter 51 . In an example of SEC AS‐MS for natural product drug discovery, a mixture of isomeric panafungins from Fusarium larvarum were screened for binding to the antifungal target polyadenosine polymerase 52 …”

Section: Size Exclusion Chromatography As‐msmentioning

confidence: 99%

“…51 In an example of SEC AS-MS for natural product drug discovery, a mixture of isomeric panafungins from Fusarium larvarum were screened for binding to the antifungal target polyadenosine polymerase. 52 Following the approach originally reported by the van Breemen laboratory using PUF AS-MS, 16 researchers at Merck used SEC AS-MS to screen combinatorial chemical analogs in an unpurified reaction product mixture for binding to a target protein. 53 In one example, 19 compounds were prepared in one reaction vessel using amide coupling and screened without purification for binding to ERK2.…”

Section: Size Exclusion Chromatography As-msmentioning

confidence: 99%

See 1 more Smart Citation

Affinity selection–mass spectrometry for the discovery of pharmacologically active compounds from combinatorial libraries and natural products

Muchiri

Breemen

2020

J Mass Spectrom

View full text Add to dashboard Cite

Invented to address the high‐throughput screening (HTS) demands of combinatorial chemistry, affinity selection–mass spectrometry (AS‐MS) utilizes binding interactions between ligands and receptors to isolate pharmacologically active compounds from mixtures of small molecules and then relies on the selectivity, sensitivity, and speed of mass spectrometry to identify them. No radiolabels, fluorophores, or chromophores are required. Although many variations of AS‐MS have been devised, three approaches have emerged as the most flexible, productive, and popular, and they differ primarily in how ligand–receptor complexes are separated from nonbinding compounds in the mixture. These are pulsed ultrafiltration (PUF) AS‐MS, size exclusion chromatography (SEC) AS‐MS, and magnetic microbead affinity selection screening (MagMASS). PUF and SEC AS‐MS are solution‐phase screening approaches, and MagMASS uses receptors immobilized on magnetic microbeads. Because pools of compounds are screened using AS‐MS, each containing hundreds to thousands of potential ligands, hundreds of thousands of compounds can be screened per day. AS‐MS is also compatible with complex mixtures of chemically diverse natural products in extracts of botanicals and fungi and microbial cultures, which often contain fluorophores and chromophores that can interfere with convention HTS. Unlike conventional HTS, AS‐MS may be used to discover ligands binding to allosteric as well as orthosteric receptor sites, and AS‐MS has been useful for discovering ligands to targets that are not easily incorporated into conventional HTS such as membrane‐bound receptors.

show abstract

Section: Size Exclusion Chromatography As‐msmentioning

confidence: 99%

Section: Size Exclusion Chromatography As-msmentioning

confidence: 99%

Affinity selection–mass spectrometry for the discovery of pharmacologically active compounds from combinatorial libraries and natural products

Muchiri

Breemen

2020

J Mass Spectrom

View full text Add to dashboard Cite

show abstract

“…It was observed by affinity selection/mass spectrometry that the "straight" isomer, assigned as parnafungin A, binds with higher affinity to polyadenosine polymerase (PAP) compared to the "bent" structures of other parnafungins. 169 The marine sponge secondary metabolite bromobenzisoxazolone barettin 22 was identied as an antifouling agent, as it inhibits the settlement (EC 50 ¼ 15 nM) of barnacle larvae (Balanus improvisus). 9 The efficiency of this inhibition is about 60 times more potent than that of isolated structural analogues, which lack the benzisoxazolinone moiety.…”

Section: Toxicology Of Isoxazolin-5-one Derivativesmentioning

confidence: 99%

A tale of four kingdoms – isoxazolin-5-one- and 3-nitropropanoic acid-derived natural products

et al. 2017

View full text Add to dashboard Cite

Covering up to September 2016This review reports on natural compounds that derive from the isoxazolinone ring as well as the 3-nitropropanoic acid (3-NPA) moiety. These structural elements occur in compounds that have been identified in plants, insects, bacteria and fungi. In particular, plants belonging to the family of legumes produce such compounds. In the case of insects, isoxazolin-5-one and 3-NPA derivatives were found in leaf beetles of the subtribe Chrysomelina. A number of these natural products have been synthesized so far. In the case of the single compound 3-NPA, several synthetic strategies have been reported and some of the most efficient routes are reviewed. The toxicity of 3-NPA results from its ability to bind covalently to the catalytic center of succinate dehydrogenase causing irreversible inhibition of mitochondrial respiration. As a motif that is produced by many species of plants, leaf beetles and fungi, different detoxification mechanisms for 3-NPA have evolved in different species. These mechanisms are based on amide formation of 3-NPA with amino acids, reduction to β-alanine, ester formation or oxidation to malonic acid semialdehyde. The biosynthetic pathways of 3-NPA and isoxazolin-5-one moieties have been studied in fungi, plants and leaf beetles. In the case of fungi, 3-NPA derives from aspartate, while leaf beetles use essential amino acids such as valine as ultimate precursors. In the case of plants, it is supposed that malonate serves as a precursor of 3-NPA, as indicated by feeding of C-labeled precursors to Indigofera spicata. In other leguminous plants it is suggested that asparagine is incorporated into compounds that derive from isoxazolin-5-one, which was indicated byC-labeled compounds as well. In the case of leaf beetles it was demonstrated that detection of radioactivity after C-labeling from a few precursors is not sufficient to unravel biosynthetic pathways.

show abstract

“…Additionally, the parnafungins (A−D) are a further group of natural products containing the structural motif of tetrahydroxanthones. Two representatives, parnafungin A and B, have been isolated from the fermentation extract of F. larvarum in 2008.…”

Section: Introductionmentioning

confidence: 99%

Scope and Limitations of the Domino Vinylogous Aldol/oxa‐Michael Reaction

2017

View full text Add to dashboard Cite

The asymmetric, atom economic reaction of salicylaldehydes with α,β‐unsaturated aldehydes in the presence of an organocatalyst leads to chiral tricyclic chromanes. In this report, the first exploration of heteroatom‐substituted α,β‐unsaturated aldehydes is demonstrated: We present the investigation of the enantioselective domino vinylogous aldol/oxa‐Michael reaction in respect to its scope and limitations. The chiral chromanes arriving from this reaction are highly functionalized and are versatile synthetic intermediates that can further be converted into the respective tetrahydroxanthones with functionalities on the C‐4a position. A new synthetic route to a methyl ester on this position is developed starting with a p‐methoxyphenyl protected alcohol.

show abstract

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

Cited by 25 publications

References 39 publications

Affinity selection–mass spectrometry for the discovery of pharmacologically active compounds from combinatorial libraries and natural products

Affinity selection–mass spectrometry for the discovery of pharmacologically active compounds from combinatorial libraries and natural products

A tale of four kingdoms – isoxazolin-5-one- and 3-nitropropanoic acid-derived natural products

Scope and Limitations of the Domino Vinylogous Aldol/oxa‐Michael Reaction

Contact Info

Product

Resources

About