Solid-phase synthesis as a tool to create exactly defined, branched polymer vectors for cell membrane targeting

0582834 - ÚMCH 2025 RIV US eng J - Journal Article
Elter, Johanna K. - Liščáková, Veronika - Moravec, Oliver - Vragović, Martina - Filipová, Marcela - Štěpánek, Petr - Šácha, Pavel - Hrubý, Martin
Solid-phase synthesis as a tool to create exactly defined, branched polymer vectors for cell membrane targeting.
Macromolecules. Roč. 57, č. 3 (2024), s. 1050-1071. ISSN 0024-9297. E-ISSN 1520-5835
R&D Projects: GA ČR(CZ) GA21-04166S; GA MŠMT LX22NPO5102; GA MZd(CZ) NU22-03-00318
Institutional support: RVO:61389013 ; RVO:61388963
Keywords : peptoids * sequence-defined polymer * solid-phase synthesis
OECD category: Polymer science; Medicinal chemistry (UOCHB-X)
Impact factor: 5.5, year: 2022
Method of publishing: Open access
https://pubs.acs.org/doi/10.1021/acs.macromol.3c02600

Modern drug formulations often require, besides the active drug molecule, auxiliaries to enhance their pharmacological properties. Tailor-made, biocompatible polymers covalently connected to the drug molecule can fulfill this function by increasing its solubility, reducing its toxicity, and guiding it to a specific target. If targeting membrane-bound proteins, localization of the drug close to the cell membrane and its target is beneficial to increase drug efficiency and residence time. In this study, we present the synthesis of highly defined, branched polymeric structures with membrane-binding properties. One to three hydrophilic poly(ethylene oxide) or poly(2-ethyloxazoline) side chains were connected via a peptoid backbone using a two-step iterative protocol for solid-phase peptoid synthesis. Additional groups, e.g., a hydrophobic anchor for membrane attachment, were introduced. Due to the nature of solid-phase synthesis, the number and order of the side chains and additional units can be precisely defined. The method proved to be versatile for the generation of multifunctional, branched polymeric structures of molecular weights up to approximately 7000 g mol–1. The behavior of all compounds towards biological membranes and cells was investigated using liposomes as cell membrane models, HEK293 and U251-MG cell lines, and red blood cells, thereby demonstrating their potential value as drug auxiliaries with cell membrane affinity.
Permanent Link: https://hdl.handle.net/11104/0351055