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.

Investigating the interaction of anticancer drug temsirolimus with human transferrin: Molecular docking and spectroscopic approach

“…Drug protein interactions are important to investigate as there is reversible binding between majority of the drugs and proteins. The drugs that are bound are transported principally as a complex with these proteins . There are many factors which influence the binding of drug and protein, and affinity of a drug towards the protein is one such key factor that determines the circulating lifetimes and bioavailability .…”

“…The drugs that are bound are transported principally as a complex with these proteins . There are many factors which influence the binding of drug and protein, and affinity of a drug towards the protein is one such key factor that determines the circulating lifetimes and bioavailability . When there is a weak binding between drug and protein, it leads to poor division and smaller lifetimes while efficient binding reduces the amount present in plasma .…”

“…1 There are many factors which influence the binding of drug and protein, and affinity of a drug towards the protein is one such key factor that determines the circulating lifetimes and bioavailability. 1,2 When there is a weak binding between drug and protein, it leads to poor division and smaller lifetimes while efficient binding reduces the amount present in plasma. 3 In view of the fact, that there is an effect of drug binding on the pharmacokinetics of the protein, it is essential to study the binding pattern between a drug and protein and its impact on structural and functional activity of the associated protein.…”

Interaction of almond cystatin with pesticides: Structural and functional analysis

“…The smear obtained in lane D suggests the potent toxic nature of Cu(OH) 2 . The susceptibility of cystatins to chemicals has previously been reported by Shah et al It was found that almond cystatin had maximum degradation in the presence of Cu(II) hydroxide and minimum degradation in the presence of methoxyfenozide (Figure ).…”