Programmable Disulfide Formation and Oxidative Folding by Paired Electrochemical Fractions

Disulfide-rich peptides are manufactured through a network of thiol oxidation, intramolecular closure, intermolecular dimerization, and thiol-disulfide exchange. This article develops PFEP as a staged, ex situ method for delivering analytically defined oxidizing and reducing capacities to an electrode-free folding vessel. The theory does not claim that oxidation-reduction potential uniquely defines folding or that electrolysis encodes native connectivity. Sequence, conformation, thiolate availability, redox couples, concentration, and mixing remain causal. A reduced–mispaired–native kinetic network was solved with deterministic parameters. Synthetic model data predict 71.5% native topology and 12.0% mispaired material after 120 min for a pulse-and-rescue programme, compared with 52.0% and 26.0% for a static redox buffer. The numbers are planning outputs, not experimental observations. The manuscript specifies topology-resolving analytics, matched chemical controls, and a design that can reject the theory. Article type: Mechanistic theory, synthetic kinetic study, and experimental validation framework. 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.