Hydrophobic Tag-Assisted Liquid-Phase Synthesis of Tirzepatide.
Pang. Zhao-Jiong ZJ; Mao. Chuan-Yu CY; Feng. Ting-Ting TT; Dong. Lin L
Key Findings
- Liquid‑phase peptide synthesis (LPPS) can replace solid‑phase synthesis for tirzepatide
- A soluble hydrophobic tag improves solubility and reduces amino‑acid and solvent waste
- Dual protection with Cbz and Fmoc on lysine boosts overall yield
Practical Outcomes
- The method could make tirzepatide cheaper and more available in the future, but it doesn’t change how you would take or dose the drug today. For now, it’s mainly of interest to manufacturers rather than end‑users.
Summary
Scientists have found a new way to make the drug tirzepatide using a liquid‑phase method instead of the usual solid‑phase process. This new technique uses a special soluble tag and a dual protection strategy on lysine, which together give higher yields and waste less material, potentially lowering production costs.
Abstract
The synthesis of tirzepatide relies heavily on solid phase peptide synthesis (SPPS), a process that is both costly and time-consuming. In this paper, a novel soluble liquid-phase assisted (LPPS) strategy for the efficient synthesis of tirzepatide is presented. The efficacy of the method is based on the distinct solubility properties of the soluble tag, which enables high yield synthesis while significantly reducing wastage of amino acids and solvents. The construction of the side chain was achieved by a dual protection strategy utilizing both Cbz and Fmoc groups on lysine. This strategy resulted in a satisfactory improvement in overall yield.
Study Information
pubmed
2025
2025-09-10T00:00:00.000Z
10.1021/acs.orglett.5c03314
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