A spectroscopic investigation and molecular docking study on the interaction of hen egg white lysozyme with liposomes of saturated and unsaturated phosphocholines probed by an anticancer drug ellipticine

Abstract

Interaction of hen egg white lysozyme with different liposomes made of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC), 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) and 2-oleoyl-1-palmitoyl-sn-glycero-3-phosphocholine (POPC) was studied by circular dichroism (CD), steady state and time resolved fluorescence spectroscopy. We used anticancer drug ellipticine and studied its entrapment and release from liposomes upon interaction with lysozyme. The molecular docking study revealed that ellipticine preferably binds to the hydrophobic pocket of lysozyme (Kbinding = 1.09 × 10(6) M(-1)). The binding was also supported by spectroscopic evidence. Addition of lysozyme to the ellipticine impregnated liposomes caused quenching of the fluorescence intensity of ellipticine as lysozyme induces hydration and phospholipid rearrangement in the bilayers leading to the leakage of drug molecules. The extent of quenching depends on the prehydration level of liposomes. Maximum quenching took place in the DPPC liposome as it is the least hydrated while minimum quenching was observed in the DOPC liposome having the highest hydration level among all the lipids. The time resolved studies revealed that both the fast and slow lifetime components of ellipticine decrease significantly with addition of lysozyme. This fact is attributed to lysozyme induced hydration and rupture of bilayers. It is revealed that upon addition of lysozyme to liposomes, the amplitude of the fast component increases and that of the slow component decreases which imply that the drug molecules are released from liposomes and subsequent migration takes place to the aqueous phase. Molecular docking studies and fluorescence measurements indicate that ellipticine after removal from the liposome binds to the hydrophobic binding site of lysozyme.

Elucidation of Binding Mechanism of Photodynamic Therapeutic Agent Toluidine Blue O with Chicken Egg White Lysozyme by Spectroscopic and Molecular Dynamics Studies

“…Conformational changes in lysozyme in the presence of TBO were carried out using CD spectral studies in far and near‐UV CD regions. The CD spectrum of native lysozyme shows characteristic bands at 208 nm and 222 nm in the far‐UV region (Fig. A).…”

“…It has been previously reported that TBO when used as a mouth rinse may get released into the environment which in turn might produce adverse effects in fish and other aquatic life . Recently, the binding of drugs with lysozyme has been studied extensively by many groups and which explore the actual interaction and binding site of drugs in protein cavity . Therefore, the precise binding characteristics of antitumor drug (TBO) with lysozyme are critical to understanding its pharmaco‐ and toxicokinetics at the site of its action.…”

Chelerythrine–lysozyme interaction: spectroscopic studies, thermodynamics and molecular modeling exploration

“…[19][20][21] Other activities include anti-inflammatory, antiviral, antiseptic, antihistamine, and antineoplastic effects. [25][26][27][28] Such studies are important for the development of small molecules that can act as effective inhibitors of the aggregation of amyloidogenic proteins. [22][23][24][25] The details of the structure of Lyz, domains and amino acids in the protein have been described in detail in a recent study.…”

Curcumin binds to the pre-fibrillar aggregates of Cu/Zn superoxide dismutase (SOD1) and alters its amyloidogenic pathway resulting in reduced cytotoxicity

“…The docking simulations were performed considering rigid macromolecule (SOD1 dimer/monomer) and a flexible ligand (curcumin) [48]. The binding site of curcumin was recognized using blind docking [49][50][51] by setting the grid size to 126 × 126 × 126 along the X, Y and Z axis respectively with 0.564 Å grid spacing. Lamarckian Genetic Algorithm (LGA) as implemented in Autodock software [52] was utilized for prediction of the binding mode.…”