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Quality not Quantity: The Role of Marine Natural Products in Drug Discovery and 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.


Epifluorescence micrographs of PS resins (100× magnification, 450–490 nm bandpass excitation filter, 520 nm low pass emission filter). (a) Underivatised PS resin as viewed under phase contrast illumination. (b) Underivatised PS resin treated with congo red (control). (c) Bromomethylated PS resin treated with congo red (14). (d) Underivatised PS resin treated with fluorescein-NHS (control). (e) PS-NH2 resin treated with fluorescein-NHS (16). (f) PS-PEG-NH2 resin treated with fluorescein-NHS (20).
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f10-marinedrugs-03-00036: Epifluorescence micrographs of PS resins (100× magnification, 450–490 nm bandpass excitation filter, 520 nm low pass emission filter). (a) Underivatised PS resin as viewed under phase contrast illumination. (b) Underivatised PS resin treated with congo red (control). (c) Bromomethylated PS resin treated with congo red (14). (d) Underivatised PS resin treated with fluorescein-NHS (control). (e) PS-NH2 resin treated with fluorescein-NHS (16). (f) PS-PEG-NH2 resin treated with fluorescein-NHS (20).

Mentions: The three derivatised resins (Fig. 11(c,e,f)) showed a high level of fluorescence, while neither of the control resins (Fig. 11(b,d)) showed any detectable fluorescence. With the Clark protocol validated, the derivatisation reactions were repeated on the surface of PS microtitre plate wells.


Quality not Quantity: The Role of Marine Natural Products in Drug Discovery and Reverse Chemical Proteomics
Epifluorescence micrographs of PS resins (100× magnification, 450–490 nm bandpass excitation filter, 520 nm low pass emission filter). (a) Underivatised PS resin as viewed under phase contrast illumination. (b) Underivatised PS resin treated with congo red (control). (c) Bromomethylated PS resin treated with congo red (14). (d) Underivatised PS resin treated with fluorescein-NHS (control). (e) PS-NH2 resin treated with fluorescein-NHS (16). (f) PS-PEG-NH2 resin treated with fluorescein-NHS (20).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f10-marinedrugs-03-00036: Epifluorescence micrographs of PS resins (100× magnification, 450–490 nm bandpass excitation filter, 520 nm low pass emission filter). (a) Underivatised PS resin as viewed under phase contrast illumination. (b) Underivatised PS resin treated with congo red (control). (c) Bromomethylated PS resin treated with congo red (14). (d) Underivatised PS resin treated with fluorescein-NHS (control). (e) PS-NH2 resin treated with fluorescein-NHS (16). (f) PS-PEG-NH2 resin treated with fluorescein-NHS (20).
Mentions: The three derivatised resins (Fig. 11(c,e,f)) showed a high level of fluorescence, while neither of the control resins (Fig. 11(b,d)) showed any detectable fluorescence. With the Clark protocol validated, the derivatisation reactions were repeated on the surface of PS microtitre plate wells.

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.