Related Experiment Video
Updated: Sep 10, 2025
A Rapid and Quantitative Fluorimetric Method for Protein-Targeting Small Molecule Drug Screening
Published on: October 16, 2015
Insights into cannabinoid-HSA interactions: spectroscopic analysis and molecular docking for binding site
Sogol Meknatkhah1, Mohammad Reza Ashrafi-Kooshk1, Hossein Lanjanian2
1Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran.
Abstract:
Cannabinoids are increasingly recognized for their therapeutic potential, yet their pharmacokinetics remain poorly understood due to their high hydrophobicity and complex interactions with plasma proteins. Human serum albumin (HSA), the principal drug carrier in blood, critically influences the distribution, bioavailability, and efficacy of lipophilic compounds. In this study, we comprehensively investigated the binding interactions between HSA and six major cannabinoids (THC, CBD, CBC, CBG, THCV, and CBDV) using fluorescence spectroscopy, synchronous fluorescence scanning (SFS), circular dichroism (CD) spectroscopy, and molecular docking simulations. Fluorescence quenching analysis revealed a static quenching mechanism, supported by quenching rate constants (Kb) exceeding diffusion limits. Temperature-dependent studies and van't Hoff analysis indicated that the interactions were driven primarily by hydrophobic forces, as evidenced by positive entropy and enthalpy changes. CD spectral analysis showed that most cannabinoids induced minimal or stabilizing effects on HSA's α-helical structure, with the exception of CBDV and CBG, which caused more pronounced, concentration-dependent secondary structure changes. Molecular docking localized the binding sites predominantly within Sudlow's sites I, involving key hydrophobic residues such as Ile, Leu, Val and Ala. Together, these findings provide new molecular insights into the transport properties of cannabinoids and highlight the role of albumin in modulating their pharmacokinetic profiles, offering valuable guidance for therapeutic drug design and delivery strategies.
More Related Videos
08:31Biosensor-based High Throughput Biopanning and Bioinformatics Analysis Strategy for the Global Validation of Drug-protein Interactions
Published on: December 1, 2020
08:49Incorporating Target Protein Structure Flexibility and Dynamics in Computational Drug Discovery Using Ensemble-Based Docking Analysis
Published on: June 20, 2025
Related Concept Videos
01:30Drug Binding to Blood Components
HSA is the most abundant plasma protein and is vital in drug binding. It contains distinct drug-binding sites, with different drugs exhibiting affinity for specific sites. There are three main drug-binding domains for HSA: sites I, II, and III. These domains are...
01:22Protein-Drug Binding: Determination Methods
Indirect methods involve isolating the bound drug from its free form in biological samples such as blood, serum, or plasma. These techniques aim to measure the percentage of drugs bound to proteins. Equilibrium dialysis is a commonly used method where the free drug concentration at equilibrium is measured by separating the bound...
02:18The Equilibrium Binding Constant and Binding Strength
01:16Protein-Drug Binding: Mechanism and Kinetics
Various forces drive these interactions, including hydrogen bonds, hydrophobic interactions, ionic bonds, electrostatic interactions, and van der Waals forces. These bonds enable drugs to bind to specific sites on proteins,...
01:20Factors Affecting Protein-Drug Binding: Protein-Related Factors
The physicochemical properties of a drug play a significant role in its ability to bind to proteins. Lipophilic drugs, which dissolve in fats, oils, and lipids, can be...
02:40Ligand Binding Sites
Protein-ligand interactions are quite specific; even though numerous potential ligands surround a cellular protein at any given time, only a particular ligand can bind to that protein. Moreover, a ligand binds only to a dedicated area on the surface of the protein, known as the...