Engineering the Tumor Surface: Synthetic Nutrient Mimicry Peptides as Stable Extracellular Anchors for Precision Cancer Therapy

This project introduces a conceptual framework for a proposed modular synthetic biology platform based on synthetic nutrient mimicry peptides (SNMPs). These lipid-anchored molecules are designed to preferentially insert into tumor cell membranes by exploiting differences in metabolism and membrane biophysics between malignant and normal tissue. Once anchored, SNMPs may serve as extracellular docking sites for engineered, non-replicative bacteriophages or virus-like particles (VLPs) carrying therapeutic payloads. The present study is explicitly scoped to the initial membrane anchoring mechanism as a necessary first step in establishing targeting specificity. All conclusions are limited to initial positional feasibility as assessed through static membrane packing analysis; no dynamic simulations or experimental validation were performed. Using CHARMM-GUI Membrane Builder, four SNMP constructs—three lipidated variants and one non-lipidated control—were positioned in a tumor-mimetic POPC/POPS/Cholesterol bilayer at pH 6.5. Static packing output was analyzed for palmitoyl chain depth relative to the bilayer midplane, peptide orientation, and conformation type. SNMP A demonstrated the deepest initial insertion (palmitoyl terminal carbons at approximately −12 to −14 Å relative to the midplane), SNMP C showed partial and angled positioning (−5 to −8 Å), SNMP B remained solvent-exposed despite lipidation, and the non-lipidated control showed no membrane association. These findings provide a plausible structural basis for selective SNMP insertion and motivate future molecular dynamics simulations and experimental validation.