Dj. Trepanier et al., Study of FK-binding protein : FK506-metabolite complexes by electrospray mass spectrometry: Correlation to immunosuppressive activity, THER DRUG M, 21(3), 1999, pp. 274-280
Electrospray ionization mass spectrometry was used to study several noncova
lent FK-binding protein (FKBP) immunosuppressant complexes in the gas phase
. Relative FKBP binding affinities were determined from the signal ratio fo
r the 7(+) charge states of bound and unbound complexes as a function of ca
pillary exit voltage. All complexes displayed a 1:1 binding stoichiometry.
The relative gas-phase binding affinities were found to be well correlated
with in vitro FKBP binding and in vitro immunosuppression (rapamycin > FK50
6 greater than or equal to 31-demethyl FK506 > 13-demethyl FK506 much great
er than Cyclosporin A; CsA). The method demonstrates potential as a simple,
rapid, and automatable technique for prediction of the immunosuppressive a
ctivity of FKBP:drug complexes.