title: Binding mechanism of the tyrosine-kinase inhibitor nilotinib to human serum albumin determined by 1H STD NMR, 19F NMR, and molecular modeling.
abstract: Drug interaction with albumins significantly affects in vivo drug transport and biological metabolism. To gain insight into the binding mechanisms of tyrosine-kinase inhibitor nilotinib (NIL) to human serum albumin (HSA), an approach combining (1)H saturation-transfer difference (STD) nuclear magnetic resonance (NMR) spectroscopy, (19)F NMR spectroscopy, steady-state fluorescence quenching, and molecular modeling was adopted. (19)F NMR was used to determine the binding constant, and a value of 4.12 × 10(3)M(-1) was obtained. Fluorescence spectroscopy was also used to determine the binding constant, and the value obtained was within the same order of magnitude. The binding process was mainly driven by hydrogen bonds and van der Waals forces. Displacement experiments further showed that NIL mainly bound to the hydrophobic cavity of HSA's subdomain IIA, also called Sudlow's site I. Molecular docking simulation was also used to establish a molecular binding model, and findings were consistent with those of displacement and the (1)H STD NMR experiments.
authors.affiliation: College of Chemical Engineering, Sichuan University, Chengdu 610065 Sichuan, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Yan
authors.affiliation: College of Chemical Engineering, Sichuan University, Chengdu 610065 Sichuan, China.
authors.forename: Di
authors.initials: D
authors.lastname: Wu
authors.affiliation: Key Laboratory of Functional Polymer Materials of the Ministry of Education, Nankai University, Tianjin 300071, China.
authors.forename: Pingchuan
authors.initials: P
authors.lastname: Sun
authors.affiliation: College of Chemical Engineering, Sichuan University, Chengdu 610065 Sichuan, China.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Ma
authors.affiliation: College of Chemical Engineering, Sichuan University, Chengdu 610065 Sichuan, China.
authors.forename: Lili
authors.initials: L
authors.lastname: Wang
authors.affiliation: College of Chemical Engineering, Sichuan University, Chengdu 610065 Sichuan, China.
authors.forename: Shanshan
authors.initials: S
authors.lastname: Li
authors.affiliation: College of Chemical Engineering, Sichuan University, Chengdu 610065 Sichuan, China.
authors.forename: Kailin
authors.initials: K
authors.lastname: Xu
authors.affiliation: College of Chemical Engineering, Sichuan University, Chengdu 610065 Sichuan, China. Electronic address: lihuilab@sina.com.
authors.forename: Hui
authors.initials: H
authors.lastname: Li
mesh_terms: D006801:Humans; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008958:Models, Molecular; D011485:Protein Binding; D047428:Protein Kinase Inhibitors / Q000378:metabolism*; D011743:Pyrimidines / Q000378:metabolism*; D012709:Serum Albumin / Q000378:metabolism*; D013050:Spectrometry, Fluorescence
chemical_list: D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D012709:Serum Albumin; C498826:nilotinib
keywords: Binding; Fluorescence spectroscopy; Human serum albumin; Molecular docking; NMR spectroscopy; Nilotinib