title: Differential effects of anti-cancer and anti-hepatitis drugs on liver cystatin.
abstract: The drug-protein interaction has been the subject of increasing interest over the decades. In the present communication, the interaction of liver cystatin with anti-cancer (adriamycin) and anti-hepatitis (adevofir dipivoxil) drugs was studied by thiol-protease inhibitory assay, UV absorption, fluorescence spectroscopy and circular dichroism (CD). A static type of quenching was observed between the protein and the drug molecules. Binding constant (Ka) of adriamycin to liver cystatin (LC) was found to be 1.08 × 10(6) M(-1). Moreover, binding site number was found to be 2. Importantly, cystatin loses its activity in the presence of adriamycin. However, intrinsic fluorescence studies in the presence of adevofir dipivoxil showed enhancement in the fluorescence intensity suggesting that binding of adevofir to LC caused unfolding of the protein. The unfolding of the test protein was also accompanied by significant loss of inhibitory activity. CD spectroscopy result showed, both adriamycin and adevofir dipivoxil caused perturbation in the secondary structure of liver cystatin. The possible implications of these results will help in combating drug induced off target effects.
authors.affiliation: Department of Biochemistry, SKIMS Medical College, Srinagar, India.
authors.forename: Aaliya
authors.initials: A
authors.lastname: Shah
authors.affiliation: Department of Medicine, Division of Endocrinology, Metabolism and Molecular Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
authors.forename: Medha
authors.initials: M
authors.lastname: Priyadarshini
authors.affiliation: Department of Biochemistry, Protein Research Chair, College of Science, King Saud University, Riyadh, Saudi Arabia.
authors.forename: Mohd Shahnawaz
authors.initials: MS
authors.lastname: Khan
authors.affiliation: Department of Biochemistry, Faculty of Life Sciences, AMU, Aligarh, India.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Aatif
authors.affiliation: Department of Biochemistry, Faculty of Life Sciences, AMU, Aligarh, India.
authors.forename: Fakhra
authors.initials: F
authors.lastname: Amin
authors.affiliation: King Fahd Medical Research Center, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
authors.forename: Shams
authors.initials: S
authors.lastname: Tabrez
authors.affiliation: Department of Haematology, Faculty of Medicine, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
authors.forename: Galila F
authors.initials: GF
authors.lastname: Zaher
authors.affiliation: Department of Biochemistry, Faculty of Life Sciences, AMU, Aligarh, India.
authors.forename: Bilqees
authors.initials: B
authors.lastname: Bano
keywords: ADR, adriamycin; Adevofir dipivoxil; Adriamycin; CD, circular dichroism; Fluorescence; HBV, human hepatitis B virus; Ka, binding constant; LC, liver cystatin; Liver cystatin; UV-spectroscopy