PFEP-Guided Manufacture of Cagrilintide: Integrating a Cys2–Cys7 Loop with N-Terminal C20 Lipidation

Cagrilintide is a 37-residue, C-terminally amidated, lipidated amylin analogue containing a Cys2–Cys7 disulfide and an N-terminal Lys bearing a γ-glutamyl-linked C20 fatty diacid. Its manufacture couples long-chain assembly, lipid-associated solubility constraints, a single intramolecular disulfide, aggregation risk, and purification of closely related acylated impurities. This article proposes a PFEP sequence in which peptide-free fractions condition dissolution, support limited oxidation, permit a brief exchange/rescue interval, and prepare the product for chromatography. The electrochemical cell does not contain cagrilintide. Synthetic process modelling predicts 89.8% correctly closed soluble monomer at the folding endpoint versus 76.9% under a static comparator, with dimer reduced from 8.7% to 3.1%. These are hypothetical values. The article defines the structure, process order, impurity map, analytical proof, and experiments required to determine whether PFEP adds value beyond matched conventional chemistry. Article type: Target-specific mechanistic hypothesis with synthetic process data. All numerical results labelled synthetic or modelled are hypothesis-illustration and planning outputs, not experimental measurements. No wet-laboratory experiment, validated process, clinical benefit, or shelf life is claimed.