title: Screening derivatized peptide libraries for tight binding inhibitors to carbonic anhydrase II by electrospray ionization-mass spectrometry.
abstract: This paper describes the use of electrospray ionization-mass spectrometry (ESI-MS) to screen two libraries of soluble compounds to search for tight binding inhibitors for carbonic anhydrase II (EC 4.2.1.1). The two libraries, H2NO2SC6H4C(O)NH-AA1-AA2-C(O)NHCH2CH2CO2H where AA1 and AA2 are L-amino acids (library size: 289 compounds) or D-amino acids (256 compounds), were constructed by attaching tripeptides to the carboxyl group of 4-carboxybenzenesulfonamide. Screening of both libraries yielded, as the tightest binding inhibitor, compound 1 (AA1 = AA2 = L-Leu; binding constant Kb = 1.4 x 10(8) M-1). The ability of ESI-MS to estimate simultaneously the relative binding affinities of a protein to soluble ligands in a library, if general, should be useful in drug development.
authors.affiliation: Department of Chemistry, Harvard University, Cambridge, Massachusetts 02138, USA.
authors.forename: J
authors.initials: J
authors.lastname: Gao
authors.forename: X
authors.initials: X
authors.lastname: Cheng
authors.forename: R
authors.initials: R
authors.lastname: Chen
authors.forename: G B
authors.initials: GB
authors.lastname: Sigal
authors.forename: J E
authors.initials: JE
authors.lastname: Bruce
authors.forename: B L
authors.initials: BL
authors.lastname: Schwartz
authors.forename: S A
authors.initials: SA
authors.lastname: Hofstadler
authors.forename: G A
authors.initials: GA
authors.lastname: Anderson
authors.forename: R D
authors.initials: RD
authors.lastname: Smith
authors.forename: G M
authors.initials: GM
authors.lastname: Whitesides
mesh_terms: D000595:Amino Acid Sequence; D002257:Carbonic Anhydrase Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D002256:Carbonic Anhydrases / Q000187:drug effects*; D005583:Fourier Analysis; D013058:Mass Spectrometry / Q000379:methods*; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D002257:Carbonic Anhydrase Inhibitors; D010455:Peptides; D002256:Carbonic Anhydrases