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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.


Photografting of glycidylmethacrylate onto PS microtitre plates using UV light in the presence of a benzophenone photoinitiator [52].
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f7-marinedrugs-03-00036: Photografting of glycidylmethacrylate onto PS microtitre plates using UV light in the presence of a benzophenone photoinitiator [52].

Mentions: Eckert and colleagues used photografting to introduce epoxide groups onto the surface of PS [52]. Initially, a methanolic solution of glycidylmethacrylate was added to the wells of a PS microtitre plate and the plate was exposed to UV light, using benzophenone as a photoinitiator. This resulted in poly(glycidylmethacrylate) being grafted to the plate surface (Fig. 7). The immobilised epoxide groups could then react with a nucleophile of choice (amine, thiol, alcohol). Similarly, Larsson et al. introduced carboxyl groups on the surface of PS plates by photografting crotonic acid using radiation from a 60Co source [53, 54]. The carboxyl-modified polymer surface was used to immobilise various human antibodies via EDC-mediated amide bond formation.


Quality not Quantity: The Role of Marine Natural Products in Drug Discovery and Reverse Chemical Proteomics
Photografting of glycidylmethacrylate onto PS microtitre plates using UV light in the presence of a benzophenone photoinitiator [52].
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f7-marinedrugs-03-00036: Photografting of glycidylmethacrylate onto PS microtitre plates using UV light in the presence of a benzophenone photoinitiator [52].
Mentions: Eckert and colleagues used photografting to introduce epoxide groups onto the surface of PS [52]. Initially, a methanolic solution of glycidylmethacrylate was added to the wells of a PS microtitre plate and the plate was exposed to UV light, using benzophenone as a photoinitiator. This resulted in poly(glycidylmethacrylate) being grafted to the plate surface (Fig. 7). The immobilised epoxide groups could then react with a nucleophile of choice (amine, thiol, alcohol). Similarly, Larsson et al. introduced carboxyl groups on the surface of PS plates by photografting crotonic acid using radiation from a 60Co source [53, 54]. The carboxyl-modified polymer surface was used to immobilise various human antibodies via EDC-mediated amide bond formation.

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.