Total solid-phase synthesis and structural elucidation of sovateltide

Abstract

Sovateltide (IRL-1620, PMZ-1620), a synthetic endothelin-1 analog, is a promising therapeutic agent for acute ischemic stroke. This study details the total solid-phase Peptide synthesis (SPPS) of Sovateltide and its subsequent structural elucidation. SPPS relies on the repetitive cycles of deprotection, coupling, and washing the 14-amino acid peptide chain on a solid support. Following cleavage from the resin and deprotection of side chain functionalities, Sovateltide was purified to homogeneity using preparative high-performance liquid chromatography (Prep HPLC). The Sovateltide successful synthesis and purification was achieved with overall yields∼28 % and product purity of ≥98 % at 13.8 mmol scale. Structural confirmation was achieved using mass spectrometry, NMR, and CD spectroscopy analysis. LCMS analysis confirmed the amino acid sequence, while 2D NMR data validated its structure. The secondary structure estimation was confirmed through CD spectroscopy.