First Gram-Scale Convergent Synthesis of Tirzepatide Using Hybrid Manufacturing | Research

The takeaway

A convergent hybrid synthesis of tirzepatide achieved gram-scale production using tangential flow filtration for fragment assembly, overcoming limitations of traditional solid-phase peptide synthesis.

Gram-scale breakthrough
A convergent hybrid approach achieved the first gram-scale tirzepatide synthesis, potentially enabling more affordable production of this blockbuster drug

What the researchers found

Convergent hybrid synthesis using SPPS fragment preparation + TFF-based assembly achieved gram-scale tirzepatide production, overcoming scalability limitations of traditional synthesis.

Why it matters

Tirzepatide demand is surging globally. More efficient manufacturing reduces costs and ensures supply for millions of patients.

How the study worked

Fragment-based convergent SPPS with tangential flow filtration for fragment coupling and purification, achieving gram-scale tirzepatide with characterization.

What this study cannot tell us

Gram-scale (not kilogram). Specific purity/yield metrics in full paper. TFF optimization needed for larger scales.

How to read the evidence

Synthetic chemistry process development. Demonstrated scalability advance.

When this study was published

Published in 2025.

The bigger picture

Scalable peptide manufacturing is essential for the GLP-1 drug revolution. This convergent approach could be applied to other complex therapeutic peptides.

Questions still open

Could this approach achieve kilogram-scale tirzepatide production?
How does cost compare to current commercial synthesis?
Would this method work for other long therapeutic peptides?

Common questions

Why is tirzepatide hard to make?

It's a 39-amino acid peptide — too long for efficient single-step synthesis. This study solved this by making it in fragments and assembling them, achieving gram-scale production for the first time.

Could this make tirzepatide cheaper?

Potentially. More efficient manufacturing reduces production costs. As GLP-1 drug demand skyrockets, scalable synthesis is essential for affordable access.

Read the original research

A Convergent Hybrid Gram-Scale Synthesis of Tirzepatide: Tangential Flow Filtration Assisted Native Chemical Ligation-Desulfurization Approach.

Angewandte Chemie (International ed. in English), 65(6), e20060

View on PubMed ↗Publisher’s paper ↗

Citation

Jalan, Ankur; Murzinski, Emily S; Jansen, Patrick J; Miller, Richard D; Embry, Matthew C; Scherer, Roger B; Moomaw, John F; Williams, Katerina M; Fisher, Cyrus A; James, Jinju; Arbour, Christine A; Guinn, Emily J; Teng, Jing; Kopach, Michael E. (2026). A Convergent Hybrid Gram-Scale Synthesis of Tirzepatide: Tangential Flow Filtration Assisted Native Chemical Ligation-Desulfurization Approach.. Angewandte Chemie (International ed. in English), 65(6), e20060. https://doi.org/10.1002/anie.202520060