An Integrative PFEP Theory for Programmable Aqueous Processing of Long Lipidated Linear Peptides
Year: 2026
Type: preprint
Abstract: Long lipidated linear peptides combine polyelectrolyte behavior with amphiphilic self-association. The lipid appendage extends exposure in vivo but can narrow the pH-solubility domain, stabilize oligomers, increase surface affinity, and complicate membrane processing. This article formulates a PFEP theory for semaglutide-, tirzepatide-, retatrutide-, survodutide-, and related sequence classes. The state vector comprises pH-capacity, ionic composition, dissolved gases, redox-active impurities, state age, peptide charge, lipid architecture, concentration, surface-area exposure, and mixing time. Five dimensionless groups describe ionization distance from pI, amphiphilic loading, mixing-to-association competition, surface capacity, and state decay. A synthetic cross-molecule dataset predicts a median 9.6 percentage-point increase in soluble monomer recovery for staged processing, but chemical reconstruction reproduces 8.9 points. The platform claim therefore concerns programmable delivery and reproducibility, not unique water structure. Prospective external validation and leave-one-peptide-out testing are specified. Article type: Integrative theory, comparative synthetic dataset, and platform validation strategy. 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.
Author: Kan, Ilyan
Institution: University of Toronto
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W7221979765
Cites:
Cited by:
Related to: