Green and efficient synthesis strategy of Tirzepatide based on fragments (AA1-14, AA15-21, AA22-29, and AA30-39)
Publish Time:
2025-09-05
Tirzepatide, as the first and only clinically applied GIP/GLP-1 receptor co-agonist, shows remarkable efficacy in the comprehensive management of type 2 diabetes, offering superior glucose lowering, better weight loss, and multidimensional metabolic benefits. It is based on the natural GIP sequence, modified through fatty acid acylation technology and amino acid sequence engineering. It is a linear peptide containing 39 amino acids, with a molecular size similar to GIP and GLP-1. The initial amino acid sequence is derived from human GIP, retaining 9 homologous amino acids of GIP and 10 amino acids common to both GIP and GLP-1.
1. Fragment Preparation: Generation of High-Purity Core Modules
Using the EMPHASES new liquid-phase peptide synthesis platform, four key fragments with purity reaching 90-95% can be synthesized, namely AA1-14, AA15-21, AA22-29, and AA30-39 fragments. These fragments serve as the core foundational modules for subsequent synthesis.
Tirzepatide Fragment 6 Tirzepatide Frag AA1-14 Purity ≥90%
CAS No.: 2656383-25-2; Molecular Formula: C₁₂₁H₁₈₁N₁₃O₂₇ Molecular Weight: 2114.64
Tirzepatide Fragment 5 Tirzepatide Frag AA15-21 Purity ≥90%
CAS No.: 2656383-24-1; Molecular Formula: C₁₀₉H₁₇₆N₁₄O₂₇; Molecular Weight: 2249.8
Tirzepatide Fragment 3 Tirzepatide Frag AA22-29 Purity ≥95%
CAS No.: 2461524-68-3; Molecular Formula: C₈₆H₁₀₀N₁₀O₁₄ Molecular Weight: 1497.77
Tirzepatide Fragment 2 Tirzepatide Frag AA30-39 Purity ≥95%
CAS No.: 2656383-23-0; Molecular Formula: C48H81N11O13.C2F3O2 Molecular Weight: 1134.25
2. Liquid-Phase Coupling Synthesis and Membrane-Assisted Separation and Purification: Fragment Purity Optimization
Fragments 7 and 4 are synthesized separately via liquid-phase coupling technology, and purified using membrane-assisted separation technology to effectively remove impurities, obtaining high-purity fragments that lay a solid quality foundation for the final synthesis.
3. Final Coupling and Peptide Formation: Construction of the Complete Peptide Chain
The purified fragments 7 and 4 are coupled in liquid phase to form a fully protected peptide chain. After subsequent processing, the final tirzepatide is obtained.
