Mazdutide (IBI-362, LY-3305677) peptide (TFA removed)

• COA/MS/HPLC Report
• Handling and Storage of Synthetic Peptides
• Material Safety Data Sheets (MSDS)

Batch to batch variation of the purity

Mazdutide (IBI-362/LY-3305677) is a synthetic peptide analogue of mammalian oxyntomodulin (OXM), engineered to activate both glucagon-like peptide-1 (GLP-1) and glucagon receptors. The peptide incorporates a fatty-acyl moiety to prolong its half-life, enabling once-weekly administration. In vitro studies demonstrate its potent binding to human and mouse GLP-1 and glucagon receptors. Evaluations in mice revealed that Mazdutide improves glucose control, reduces body weight, and increases energy expenditure, even in Gcgr knockout and Glp1r knockout models.

Structurally, Mazdutide is designed to balance the activation of GLP-1 and glucagon receptors, aiming to avoid glucagon-induced hyperglycemia while maintaining metabolic benefits. Its dual agonist activity mimics the physiological effects of OXM, which modulates energy expenditure and appetite through glucagon and GLP-1 receptor pathways, respectively. The peptide's pharmacokinetic profile shows slow absorption, with a median time to peak concentration (T_max) of approximately 72 hours and an extended half-life ranging from 6.1 to 28.1 days, supporting its once-weekly dosing regimen.

• N Engl J Med. 2025 Jun 12;392(22):2215-2225. doi: 10.1056/NEJMoa2411528. Epub 2025 May 25. PMID: 40421736.
• Nat Commun. 2022 Jun 24;13(1):3613. doi: 10.1038/s41467-022-31328-x. PMID: 35750681; PMCID: PMC9232612.

Trifluoroacetic acid (TFA) has a significant impact on peptides due to its role in the peptide synthesis process.

TFA is essential for the protonation of peptides that lack basic amino acids such as Arginine (Arg), Histidine (His), and Lysine (Lys), or ones that have blocked N-termini. As a result, peptides often contain TFA salts in the final product.

TFA residues, when present in custom peptides, can cause unpredictable fluctuations in experimental data. At a nanomolar (nM) level, TFA can influence cell experiments, hindering cell growth at low concentrations (as low as 10 nM) and promoting it at higher doses (0.5–7.0 mM). It can also serve as an allosteric regulator on the GlyR of glycine receptors, thereby increasing receptor activity at lower glycine concentrations.

In an in vivo setting, TFA can trifluoroacetylate amino groups in proteins and phospholipids, inducing potentially unwanted antibody responses. Moreover, TFA can impact structure studies as it affects spectrum absorption.