title: Screening a natural product-based combinatorial library using FTICR mass spectrometry.
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.
authors.affiliation: Chemical Biology Group, Eskitis Institute for Cell and Molecular Therapies, Griffith University, Nathan Campus, Brisbane 4111, Australia. s.poulsen@griffith.edu.au
authors.forename: Sally-Ann
authors.initials: SA
authors.lastname: Poulsen
authors.forename: Rohan A
authors.initials: RA
authors.lastname: Davis
authors.forename: Timothy G
authors.initials: TG
authors.lastname: Keys
mesh_terms: D000818:Animals; D001688:Biological Products / Q000737:chemistry* / Q000378:metabolism; D024402:Carbonic Anhydrase II / Q000378:metabolism; D002417:Cattle; D020650:Combinatorial Chemistry Techniques; D013058:Mass Spectrometry; D017550:Spectroscopy, Fourier Transform Infrared / Q000379:methods*; D013329:Structure-Activity Relationship
chemical_list: D001688:Biological Products; D024402:Carbonic Anhydrase II