jm960013g_si_001.pdf (200.05 kB)
Download fileScreening Derivatized Peptide Libraries for Tight Binding Inhibitors to Carbonic Anhydrase II by Electrospray Ionization-Mass Spectrometry
journal contribution
posted on 1996-05-10, 00:00 authored by Jinming Gao, Xueheng Cheng, Ruidan Chen, George B. Sigal, James E. Bruce, Brenda L. Schwartz, Steven A. Hofstadler, Gordon A. Anderson, Richard D. Smith, George M. WhitesidesThis 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
(1),
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
× 108 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.