Signaling Modulation via Minimal C-Terminal Modifications of Apelin-13.

ABSTRACT: Apelin is an endogenous peptide that is involved in many diseases such as cardiovascular diseases, obesity, and cancer, which has made it an attractive target for drug discovery. Herein, we explore the penultimate and final sequence positions of [Pyr¹]-apelin-13 (Ape13) via C-terminal N _α-alkylated amide bonds and the introduction of positive charges, potentially targeting the allosteric sodium pocket, by assessing the binding affinity and signaling profiles at the apelin receptor (APJ). Synthetic analogues modified within this segment of Ape13 showed high affinity (K _i 0.12-0.17 nM vs Ape13 K _i 0.7 nM), potent Gα_i1 activation (EC₅₀ Gα_i1 0.4-0.9 nM vs Ape13 EC₅₀ 1.1 nM), partial ago

SUBMITTER: Theroux L 

PROVIDER: S-EPMC9926529 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature