Opioid/Dopamine Receptor Binding Studies, NMR and Molecular Dynamics Simulation of LENART01 Chimera, an Opioid-Bombesin-like Peptide.

Serafin, Pawel; Szeleszczuk, Łukasz; Zhukov, Igor; Szűcs, Edina; Gombos, Dávid; Stefanucci, Azzurra; Mollica, Adriano; Pisklak, Dariusz Maciej; Kleczkowska, Patrycja

The design and development of hybrid compounds as a new class of drug candidates remains an excellent opportunity to improve the pharmacological properties of drugs (including enzymatic stability, efficacy and pharmacokinetic and pharmacodynamic profiles). In addition, considering various complex diseases and/or disorders, the conjugate chemistry approach is highly acceptable and justified. Opioids have long been recognized as the most potent analgesics and serve as the basic pharmacophore for potent hybrid compounds that may be useful in pain management. However, a risk of tolerance and physical dependence exists. Since dopamine receptors have been implicated in the aforementioned adverse effects of opioids, the construction of a hybrid with dual action at opioid and dopamine receptors is of interest. Herein, we present nuclear magnetic resonance (NMR) spectroscopy and molecular dynamics simulation results for LENART01, an opioid–ranatensin hybrid peptide. Apart from molecular docking, protein–ligand interactions were also assessed in vitro using a receptor binding assay, which proved LENART01 to be bound to mu-opioid and dopamine receptors, respectively.

OPIOID receptors; MOLECULAR dynamics; DOPAMINE receptors; PEPTIDES; BINDING site assay; MOLECULAR spectroscopy; PROTEIN-ligand interactions

Molecules, 2024, Vol 29, Issue 1, p272

1420-3049

Academic Journal

10.3390/molecules29010272