title: Role of the conformational flexibility of evodiamine in its binding to protein hosts: a comparative spectroscopic and molecular modeling evaluation with rutaecarpine.
abstract: Spectroscopic studies combined with computational analysis indicate the inherent conformational flexibility of the β-carbolin derivative evodiamine (EVD) featured with diverse pharmacological activities. Qualitative evaluation of the circular dichroism (CD) spectra of EVD enantiomers complemented with quantum chemical calculations reveals a chiral exciton signature that can be assigned to the folded, L-shaped conformation of the molecule. Changes of the exciton couplet measured in different solvents and the near-UV CD profile upon binding to human serum albumin (HSA) refer to the structural adaptability of EVD. The enantioselectivity of EVD-HSA interaction is demonstrated showing the binding preference of the (R)-enantiomer. Comparison of experimental and calculated CD spectra of various conformers of EVD as well as the results of molecular docking data suggest that the (R)-antipode is accomodated within the IIA subdomain of HSA in ridge-tile conformation. Rutaecarpine (RTC), the close congener of EVD, forms much tighter association complexes both with HSA and α1-acid glycoprotein. In contrast to EVD, the nearly planar geometry of the indoloquinazoline ring system of RTC allows its stacked dimeric binding to the HSA.
authors.affiliation: Research Group of Chemical Biology, Institute of Organic Chemistry, Research Centre for Natural Sciences, Hungarian Academy of Sciences, POB 289, H-1519, Budapest, Hungary. zsila.ferenc@ttk.mta.hu.
authors.forename: Celesztina
authors.initials: C
authors.lastname: Domonkos
authors.forename: Ilona
authors.initials: I
authors.lastname: Fitos
authors.forename: Júlia
authors.initials: J
authors.lastname: Visy
authors.forename: Ferenc
authors.initials: F
authors.lastname: Zsila
mesh_terms: D001665:Binding Sites; D002942:Circular Dichroism; D006801:Humans; D026121:Indole Alkaloids / Q000737:chemistry*; D008958:Models, Molecular; D062105:Molecular Docking Simulation; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011799:Quinazolines / Q000737:chemistry*; D012709:Serum Albumin / Q000737:chemistry*; D013056:Spectrophotometry, Ultraviolet; D013237:Stereoisomerism; D052999:Quinazolinones
chemical_list: D026121:Indole Alkaloids; D011799:Quinazolines; D012709:Serum Albumin; C028632:rutecarpine; D052999:Quinazolinones; C049639:evodiamine