What question did this study set out to answer?

The aim is to develop a more efficient synthesis method for Retatrutide, addressing limitations of existing techniques.

June 4, 2026

A Hydrophobic Tag-Assisted Liquid-Phase Strategy for the Synthesis of Retatrutide

Key Points

The aim is to develop a more efficient synthesis method for Retatrutide, addressing limitations of existing techniques.
Utilized hydrophobic tag-assisted liquid-phase peptide synthesis (LPPS) for Retatrutide synthesis.
Compared the effectiveness and flexibility of LPPS to traditional solid-phase peptide synthesis (SPPS).
LPPS demonstrated greater efficiency and scalability in synthesizing Retatrutide compared to SPPS.
The structural flexibility of the synthesized Retatrutide improved with the LPPS method.

Abstract

Retatrutide is a novel triple agonist that targets the glucagon receptor (GCGR), the glucose-dependent insulinotropic polypeptide receptor (GIPR), and the glucagon-like peptide-1 receptor (GLP-1R). At present, its synthesis relies predominantly on solid-phase peptide synthesis (SPPS), an approach that suffers from inherent limitations in terms of efficiency, scalability, and structural flexibility. In this study, we present a novel method for the synthesis of Retatrutide, namely hydrophobic tag-assisted liquid-phase peptide synthesis (LPPS). This method provides a practical and flexible alternative to conventional SPPS for the synthesis of Retatrutide.

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