Maron, E.; Kochovski, Z.; Zuckermann, R.N.; Börner, H.G.: Peptide-Assisted Design of Peptoid Sequences: One Small Step in Structure and Distinct Leaps in Functions. ACS Macro Letters 9 (2020), p. 233-237

Using peptide sequences for the design of functional peptoids is demonstrated for a peptide-based formulation additive that was specifically tailored to solubilize the photosensitizer meta-tetra(hydroxyphenyl)-chlorin. A set of peptoid-block-poly(ethylene glycol) solubilizers with systematic sequence variations are synthesized to reveal contributions of side-chain sequence and backbone functionalities on drug hosting and release properties. The drug payload sensitively depends on the side-chain patterns, and the best performing peptoid sequence reaches 3-times higher capacity than the corresponding peptide. The peptoid backbone not only acts as a neutral scaffold but also impacts the drug release kinetics compared to the analogues peptide, by reducing the capability to assist drug transfer to blood plasma protein models.