Design, Synthesis, and <i>In Vitro</i> Characterization of Proteolytically-Stable Opioid-Neurotensin Hybrid Peptidomimetics.

ABSTRACT: Linking an opioid to a nonopioid pharmacophore represents a promising approach for reducing opioid-induced side effects during pain management. Herein, we describe the optimization of the previously reported opioid-neurotensin hybrids (OPNT-hybrids), SBL-OPNT-05 & -10, containing the μ-/δ-opioid agonist H-Dmt-d-Arg-Aba-β-Ala-NH₂ and NT(8-13) analogs optimized for NTS2 affinity. In the present work, the constrained dipeptide Aba-β-Ala was modified to investigate the optimal linker length between the two pharmacophores, as well as the effect of expanding the aromatic moiety within constrained dipeptide analogs, via the inclusion of a naphthyl moiety. Additionally, the N-terminal Arg residue of the NT(8-13) pharmacophore was substituted with β³ h<

SUBMITTER: De Neve J 

PROVIDER: S-EPMC11406707 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature