RT Journal Article
T1 Equilibrium studies of a fluorescent tacrolimus binding to surfactant protein A
A1 Cañadas, Olga
A1 Sáenz, Alejandro
A1 Orellana Moraleda, Guillermo
A1 Casals Carro, María Cristina
AB Tacrolimus (FK506) is a hydrophobic immunosuppressive agent used in kidney, liver, and lung transplantation. The objective of this study was to characterize the binding of FK506 to surfactant protein A (SP-A), an abundant lipoprotein found in the alveolar fluid that functions as part of the innate immune system in the lung. We have synthesized a novel derivative of FK506 in which a dansyl moiety was covalently bound via cadaverine to the C22 position of the FK506 molecule (DNS-FK). Using the fluorescence and anisotropy properties of DNS-FK, we demonstrated that tacrolimus avidly binds to SP-A with an apparent equilibrium association constant (K(app)) of 10(7)M(-1) and a Gibbs binding free energy of -40 kJ mol(-1)K(-1). Derivatization of FK506 at the C22 position did not block FK506 binding to the cytosolic immunophilin FK506-binding protein (FK-BP) or human serum albumin (HSA), both used as controls of tacrolimus-binding proteins. K(app) for FK-BP/DNS-FK and HSA/DNS-FK complexes were 1.5 x 10(7) and 10(7)M(-1), respectively. The high sensitivity of this analytical technique makes it suitable for binding analysis of FK506 to proteins
PB Elsevier
SN 0003-2697
YR 2005
FD 2005
LK https://hdl.handle.net/20.500.14352/93041
UL https://hdl.handle.net/20.500.14352/93041
LA eng
NO Cañadas O, Sáenz A, Orellana G, Casals C. Equilibrium studies of a fluorescent tacrolimus binding to surfactant protein A. Anal. Biochem. 2005 May 1; 340(1): 57-65. 2005
NO Ministerio de Sanidad (España)
NO Ministerio de Ciencia y Tecnología (España)
NO Fujisawa GmbH
DS Docta Complutense
RD 15 sept 2024