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Bioorg Med Chem. 2006 Jan 15;14(2):510-5. Epub 2005 Sep 29.

Screening a natural product-based combinatorial library using FTICR mass spectrometry.

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1
Chemical Biology Group, Eskitis Institute for Cell and Molecular Therapies, Griffith University, Nathan Campus, Brisbane 4111, Australia. s.poulsen@griffith.edu.au

Abstract

This manuscript reports the use of Fourier transform ion cyclotron resonance mass spectrometry to screen a combinatorially generated natural product-based library for binding affinity to bovine carbonic anhydrase II (bCAII). The fungal natural product 3-chloro-4-hydroxyphenylacetamide was the library template, with 11 secondary amide analogues of this template constituting the combinatorial library. 2-(3-Chloro-4-hydroxyphenyl)-N-(4-sulfamoylphenethyl)acetamide (compound 11) of this library was identified as a tight binding inhibitor of bCAII, by detection of a noncovalent complex corresponding to [bCAII+11] in the mass spectrum. A competitive bCAII enzyme binding assay validated the mass spectrometry screening result. The equilibrium dissociation constant (K(i)) for 11 was measured as 77.4 nM. Preliminary structure-activity investigations of the bioactive natural product analogue are also reported.

PMID:
16198579
DOI:
10.1016/j.bmc.2005.08.030
[Indexed for MEDLINE]
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