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Quality not Quantity: The Role of Marine Natural Products in Drug Discovery and Reverse Chemical Proteomics

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ABSTRACT

Reverse chemical proteomics combines affinity chromatography with phage display and promises to be a powerful new platform technology for the isolation of natural product receptors, facilitating the drug discovery process by rapidly linking biologically active small molecules to their cellular receptors and the receptors’ genes. In this paper we review chemical proteomics and reverse chemical proteomics and show how these techniques can add value to natural products research. We also report on techniques for the derivatisation of polystyrene microtitre plates with cleavable linkers and marine natural products that can be used in chemical proteomics or reverse chemical proteomics. Specifically, we have derivatised polystyrene with palau’amine and used reverse chemical proteomics to try and isolate the human receptors for this potent anticancer marine drug.

No MeSH data available.


Bromomethylation of PS and subsequent derivatisation with fluorescent probes.
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f8-marinedrugs-03-00036: Bromomethylation of PS and subsequent derivatisation with fluorescent probes.

Mentions: Cross-linked PS resin was used as a model system to evaluate the protocols described by Clark [47]. The high loading capacity of the resin (>1 mmol/g) allowed the use of fluorescent probes to follow the reactions visually (Fig. 8). Initially, PS resin was bromomethylated using the same conditions reported by Clark for PS microtitre plates. One portion of the activated resin (13) was treated with congo red (λem = 600 nm) to yield (14), while a second portion of activated resin was first converted to the aminomethylated derivative (15) and was then reacted with fluorescein-NHS (λem = 520 nm) to yield (16). Portions of the underivatised PS resin were also treated with the dyes as controls.


Quality not Quantity: The Role of Marine Natural Products in Drug Discovery and Reverse Chemical Proteomics
Bromomethylation of PS and subsequent derivatisation with fluorescent probes.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3756327&req=5

f8-marinedrugs-03-00036: Bromomethylation of PS and subsequent derivatisation with fluorescent probes.
Mentions: Cross-linked PS resin was used as a model system to evaluate the protocols described by Clark [47]. The high loading capacity of the resin (>1 mmol/g) allowed the use of fluorescent probes to follow the reactions visually (Fig. 8). Initially, PS resin was bromomethylated using the same conditions reported by Clark for PS microtitre plates. One portion of the activated resin (13) was treated with congo red (λem = 600 nm) to yield (14), while a second portion of activated resin was first converted to the aminomethylated derivative (15) and was then reacted with fluorescein-NHS (λem = 520 nm) to yield (16). Portions of the underivatised PS resin were also treated with the dyes as controls.

View Article: PubMed Central

ABSTRACT

Reverse chemical proteomics combines affinity chromatography with phage display and promises to be a powerful new platform technology for the isolation of natural product receptors, facilitating the drug discovery process by rapidly linking biologically active small molecules to their cellular receptors and the receptors’ genes. In this paper we review chemical proteomics and reverse chemical proteomics and show how these techniques can add value to natural products research. We also report on techniques for the derivatisation of polystyrene microtitre plates with cleavable linkers and marine natural products that can be used in chemical proteomics or reverse chemical proteomics. Specifically, we have derivatised polystyrene with palau’amine and used reverse chemical proteomics to try and isolate the human receptors for this potent anticancer marine drug.

No MeSH data available.