Paired-Fraction Electrochemical Programming for Arginine Vasopressin Manufacture: Charge-Aware Control of Cys¹-Cys⁶ Cyclization

Abstract

Arginine vasopressin (AVP) is a cyclic amidated nonapeptide containing a Cys1-Cys6 disulfide and a strongly basic Arg8 residue. This Perspective derives an AVP-specific implementation of paired-fraction electrochemical programming (PFEP). The divided electrochemical cell is treated as an ex situ generator of quantifiable chemical capacities; the peptide never contacts an electrode. The proposed advantage is a feedback-controlled transition from a reduced, soluble precursor state to selective intramolecular disulfide closure, followed by rapid termination and desalting. AVP differs from oxytocin by only two residues, but its Arg8-driven charge, adsorption, ion-pairing, and chromatographic behavior prevent simple transfer of an oxytocin operating window. The article specifies critical material attributes, fraction-release tests, kinetic sampling, mass-balance controls, and orthogonal confirmation of monomeric cyclic AVP. The theory predicts a target-specific trajectory rather than a universal anolyte or catholyte recipe. It is falsified as a source-specific mechanism if a chemically reconstructed trajectory gives the same molecular profile, and rejected as a process if PFEP adds no reproducibility, selectivity, waste, or operability advantage. No experimental manufacturing claim is made. Article type: Perspective, mechanistic hypothesis, and experimental framework. No experimental peptide yield, potency, clinical effect, or shelf-life evidence is reported.