Dynamic combinatorial mass spectrometry leads to metallo-beta-lactamase inhibitors.
The use of protein ESI mass spectrometry under non-denaturing conditions to analyze a dynamic combinatorial library of thiols/disulfides with the BcII metallo-beta-lactamase enabled the rapid identification of an inhibitor with a K(i) of < 1 microM. The study exemplifies the utility of protein-MS for screening dynamic mixtures of potential enzyme-inhibitors.
Liénard
Benoît M R
BM
Chemistry Research Laboratory and OCISB, Oxford, UK.
Hüting
Rebekka
R
Lassaux
Patricia
P
Galleni
Moreno
M
Frère
Jean-Marie
JM
Schofield
Christopher J
CJ
D007700:Kinetics; D008958:Models, Molecular; D021241:Spectrometry, Mass, Electrospray Ionization; D013329:Structure-Activity Relationship; D013438:Sulfhydryl Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D065093:beta-Lactamase Inhibitors; D001618:beta-Lactamases / Q000737:chemistry*
D013438:Sulfhydryl Compounds; D065093:beta-Lactamase Inhibitors; C455979:beta-lactamase BcII; D001618:beta-Lactamases