Elucidating the interactions of endocannabinoid-like neurotransmitters, N-acyltaurines and bovine serum albumin: Spectroscopic and computational approaches

Abstract

N-Acyltaurines (NATs) are endogenous neurotransmitters, structurally similar to endocannabinoids, and have anti-inflammatory and anti-proliferative effects. In response to NATs, TRP channels, TRPV1, TRPV4 and the peptide hormone, GLP-1 are activated. Serum albumin proteins act as transporters for a variety of substances in blood plasma (i.e., hormones, fatty acids, bilirubin, ions, and medications). Due to the structural closeness of Bovine Serum Albumin (BSA) and Human Serum Albumin (HSA), a study into NAT-BSA interactions is crucial. To study interactions of NATs (n = 10–18) with BSA, spectroscopic and computational techniques were used. From the steady-state fluorescence measurements, observed binding constants are in the range of 1.57 × 10⁵ M⁻¹ to 2.85 × 10⁵ M⁻¹. Due to the binding of NATs, the fluorescence of BSA is quenched (∼24.77 %). The negative enthalpy and entropy change and Gibbs free energy values, obtained from van't Hoff plot indicate that the interactions between NATs and BSA are spontaneous and primarily driven by hydrogen bonding. Competitive site-binding assays with warfarin and ibuprofen show that NATs bind to both the drug-binding sites in BSA concurrently. The CD spectroscopic and FT-IR analysis indicates relatively marginal changes in the secondary structure of BSA. Molecular docking analyses are done to identify binding locations and molecular-level interactions. The negative free energy values indicate that NATs have a positive binding relationship with BSA. These findings are congruent with the findings of site-binding studies, which reveal that NATs have a higher proclivity for interacting with sites I and II at the same time.