Peptide Helix-Y¹² as Potential Effector for Peroxisome Proliferator-Activated Receptors

Area of Science:

• Molecular biology and pharmacology
• Biochemistry and medicinal chemistry

Background:

• Peroxisome proliferator-activated receptors (PPARs) are crucial nuclear receptors regulating lipid and glucose metabolism, and immune responses.
• PPARs are therapeutic targets for metabolic diseases like dyslipidemia and non-alcoholic fatty liver disease.
• Existing synthetic PPAR ligands have side effects, necessitating the discovery of selective ligands with specific biological actions.

Purpose of the Study:

• To investigate specific components of HB-ATV-8 nanoparticles as potential ligands for PPARs.
• To evaluate the binding affinity and interaction modes of these components with PPARs using molecular docking.

Main Methods:

• Blind molecular docking simulations were employed to assess the binding of selected nanoparticle components to PPARs.
• Analysis of binding free energy (∆G _b) to determine interaction favorability.
• Detailed examination of amino acid interactions within the PPAR ligand-binding domain (LBD).

Main Results:

• Therozeaxanthins exhibited the most favorable binding interactions with PPARs, followed by the amphipathic peptide Helix-Y¹².
• Helix-Y¹² demonstrated extensive interactions within the PPAR LBD, including hydrogen bonds with key residues like Tyr314 and Tyr464 in PPARα.
• Novel interactions between Helix-Y¹² and PPAR amino acids were identified, distinct from those of known ligands.

Conclusions:

• The amphipathic peptide Helix-Y¹² and thermozeaxanthins show significant potential as novel ligands for PPARs.
• These findings suggest promising therapeutic avenues for metabolic diseases by targeting PPARs with these identified molecules.
• Further research is warranted to validate these findings and explore the therapeutic efficacy of Helix-Y¹² and thermozeaxanthins.