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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.


Derivatisation of PS microtitre plates with palau’amine via a cleavable (disulfide-containing) PEG linker.
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f11-marinedrugs-03-00036: Derivatisation of PS microtitre plates with palau’amine via a cleavable (disulfide-containing) PEG linker.

Mentions: PS microtitre plates were next derivatised with palau’amine via a cleavable PEG linker (Fig. 12). Palau’amine is a bisguanidine alkaloid, first isolated from the marine sponge Stylotella agminata by Kinnel, Gehrken and Scheuer [56]. Although its acute toxicity is relatively low, palau’amine exhibits powerful antibacterial, antifungal, antitumour and immunosuppressive activities [57]. The complex hexacyclic ring system, dense stereochemistry, high degree of functionalisation and inherent instability of the molecule makes palau’amine a challenging synthetic target [58, 59, 60, 61], and a successful total synthesis has yet to be reported. As is frequently the case with biologically active natural products, the cellular receptors for palau’amine are not known, so palau’amine is an interesting candidate for investigation by reverse chemical proteomics.


Quality not Quantity: The Role of Marine Natural Products in Drug Discovery and Reverse Chemical Proteomics
Derivatisation of PS microtitre plates with palau’amine via a cleavable (disulfide-containing) PEG linker.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f11-marinedrugs-03-00036: Derivatisation of PS microtitre plates with palau’amine via a cleavable (disulfide-containing) PEG linker.
Mentions: PS microtitre plates were next derivatised with palau’amine via a cleavable PEG linker (Fig. 12). Palau’amine is a bisguanidine alkaloid, first isolated from the marine sponge Stylotella agminata by Kinnel, Gehrken and Scheuer [56]. Although its acute toxicity is relatively low, palau’amine exhibits powerful antibacterial, antifungal, antitumour and immunosuppressive activities [57]. The complex hexacyclic ring system, dense stereochemistry, high degree of functionalisation and inherent instability of the molecule makes palau’amine a challenging synthetic target [58, 59, 60, 61], and a successful total synthesis has yet to be reported. As is frequently the case with biologically active natural products, the cellular receptors for palau’amine are not known, so palau’amine is an interesting candidate for investigation by reverse chemical proteomics.

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.