ISSN print edition: 0366-6352 ISSN electronic edition: 1336-9075 Registr. No.: MK SR 9/7 Published monthly

Insight into the binding mechanism of P2Y12-specific ligands with serum albumin by spectroscopic and computational approaches

Vijay Kumar Singh, Akansha Verma, Piyush Verma, Chandraprakash Gond, Himanshu Ojha, Mallika Pathak, and Anjani Kumar Tiwari

Babasaheb Bhimrao Ambedkar University (BBAU), Lucknow, India

E-mail: pathakmallika@gmail.com

Received: 19 December 2024  Accepted: 21 February 2026

Abstract:

The P2Y receptor is a G-protein-coupled extracellular nucleotide receptor categorized into two groups based on their ligand affinities present across different human tissues and serve diverse biological roles. These receptors are under investigation as potential therapeutic targets for numerous diseases, including pain, cardiovascular diseases, neurodegenerative disorders, and cancer. This work includes evaluating P2Y12 receptor ligands L3 and L4. Computational studies were performed to measure binding affinity and assess the interaction of L3 and L4 ligands with bovine serum albumin (BSA). Various spectroscopic techniques characterized these interactions, including UV-visible, fluorescence, and circular dichroism (CD). Synchronous spectroscopy was used to observe protein conformational changes and fluorescence quenching upon ligand binding. Spectroscopic techniques were also used to evaluate structural modifications in BSA induced by ligand interactions. Docking results confirmed that the ligand L3 exhibited a higher binding affinity at Sudlow Site I, followed by L4. This work highlights the effective binding of L3 with better binding affinity at Sudlow site I having a docking score of − 25 and binding energy of − 27 kJ/mol. L3 and L4 were also found responsible for altering the β-Sheet and α-Helix content of BSA by 1–2% signifying the complex formation of ligands with protein (BSA) which was also confirmed by substantial bathochromic shift and static quenching by both the ligands.

Graphic abstract

Keywords: Binding affinity; P2Y12 Purinergic receptor; Circular dichroism; Molecular docking; Serum-Albumin

Full paper is available at www.springerlink.com.

DOI: 10.1007/s11696-026-04764-y

Chemical Papers 80 (6) 6271–6283 (2026)