Interaction of cationic protoberberine alkaloids with human serum albumin. No spectroscopic evidence on binding to Sudlow's site 1.
Physicochemical studies on drug interactions with human serum albumin (HSA) are relevant for elucidation, at the molecular level, of the processes occurring in vivo. In this work using optical spectroscopic methods (fluorescence, absorption, circular dichroism), we have investigated aqueous HSA solutions containing pharmaceutically important isoquinoline alkaloids, berberine and palmatine. The primary objective was to verify whether the two compounds are located in the subdomain IIA of the secondary HSA structure as reported in literature. We prove that the excited state of Trp214 residue is not quenched by the alkaloids; all observed changes in fluorescence spectra are due to inner filter effects. Furthermore, differential absorption spectra indicate that the ligands remain in a waterlike microenvironment. We infer that bound alkaloid molecules are located at the protein/water interface. Yet, such binding mode can induce some unfolding of the HSA molecule detectable in the far-UV circular dichroism (CD) spectra. We have also performed, for the first time, pulse radiolysis studies of hydrated electron scavenging in the HSA/alkaloid systems and have measured steady-state absorption spectra of irradiated samples. The results reveal that neither berberine nor palmatine is effectively protected by the protein against one-electron reduction, which is consistent with the aforementioned conclusion.
Institute of Applied Radiation Chemistry, Lodz University of Technology , Wroblewskiego 15, 93-590 Lodz, Poland.
Milena
M
Marszalek
Anna
A
Konarska
Ewa
E
Szajdzinska-Pietek
Marian
M
Wolszczak
D000470:Alkaloids / Q000378:metabolism*; D001600:Berberine Alkaloids / Q000378:metabolism*; D001665:Binding Sites; D002412:Cations; D002942:Circular Dichroism; D006801:Humans; D008958:Models, Molecular; D012709:Serum Albumin / Q000378:metabolism*; D013050:Spectrometry, Fluorescence
D000470:Alkaloids; D001600:Berberine Alkaloids; D002412:Cations; D012709:Serum Albumin; C009090:protoberberine