{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T10:06:52Z","timestamp":1792058812477,"version":"4.4.0"},"reference-count":19,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2025,4,7]],"date-time":"2025-04-07T00:00:00Z","timestamp":1743984000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>This study describes the synthesis, interaction with DNA, and transfection efficacy of eight lipidated compounds based on a recently published non-lipidated parent molecule, an octamer of 2,3-l-Dap, carrying the guanidine group on its side chain. The compounds obtained were found to be non-toxic up to 5 \u00b5M and efficient DNA binders and showed greater transfection efficiency than the parent compound, with two leading molecules containing acetic and decanoic moieties. DLS experiments indicated two groups of interaction with DNA. One group modified by short-chain lipids (up to eight carbon atoms in the main chain) forms large structures due to the aggregation of multiple nucleic acids. The second group (from twelve to sixteen carbon atoms) with dominant condensation creates smaller forms and is less effective in transporting DNA into the cells.<\/jats:p>","DOI":"10.3390\/molecules30071644","type":"journal-article","created":{"date-parts":[[2025,4,23]],"date-time":"2025-04-23T20:43:17Z","timestamp":1745440997000},"page":"1644","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Lipidated DAPEG Polymers as a Non-Toxic Transfection Agent\u2014Influence of Fatty Acid Side Chain on Transfection Efficacy"],"prefix":"10.3390","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7063-8577","authenticated-orcid":false,"given":"Wiktoria","family":"Mallek","sequence":"first","affiliation":[{"name":"Faculty of Chemistry, University of Gdansk, Wita Stwosza 63, 80-308 Gdansk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anita","family":"Romanowska","sequence":"additional","affiliation":[{"name":"Faculty of Chemistry, University of Gdansk, Wita Stwosza 63, 80-308 Gdansk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wiktoria","family":"Machowicz","sequence":"additional","affiliation":[{"name":"Faculty of Chemistry, University of Gdansk, Wita Stwosza 63, 80-308 Gdansk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0086-7777","authenticated-orcid":false,"given":"Agnieszka","family":"Piwkowska","sequence":"additional","affiliation":[{"name":"Mossakowski Medical Research Institute Polish Academy of Sciences, Wita Stwosza 63, 80-308 Gdansk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8335-3431","authenticated-orcid":false,"given":"Adam","family":"Lesner","sequence":"additional","affiliation":[{"name":"Faculty of Chemistry, University of Gdansk, Wita Stwosza 63, 80-308 Gdansk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2216-5597","authenticated-orcid":false,"given":"Magdalena","family":"Wysocka","sequence":"additional","affiliation":[{"name":"Faculty of Chemistry, University of Gdansk, Wita Stwosza 63, 80-308 Gdansk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Fus-Kujawa, A., Prus, P., Bajdak-Rusinek, K., Teper, P., Gawron, K., Kowalczuk, A., and Sieron, A.L. (2021). An Overview of Methods and Tools for Transfection of Eukaryotic Cells in vitro. Front. Bioeng. Biotechnol., 9.","DOI":"10.3389\/fbioe.2021.701031"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1038\/s41578-020-00247-y","article-title":"A materials-science perspective on tackling COVID-19","volume":"5","author":"Tang","year":"2020","journal-title":"Nat. Rev. Mater."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Tan, E., Chin, C.S.H., Lim, Z.F.S., and Ng, S.K. (2021). HEK293 Cell Line as a Platform to Produce Recombinant Proteins and Viral Vectors. Front. Bioeng. Biotechnol., 9.","DOI":"10.3389\/fbioe.2021.796991"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"600","DOI":"10.1016\/j.jconrel.2022.02.010","article-title":"Current state of the art in peptide-based gene delivery","volume":"343","author":"Hadianamrei","year":"2022","journal-title":"J. Control. Release"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"4060","DOI":"10.1021\/acs.biomac.1c00697","article-title":"Polycation-Mediated Transfection: Mechanisms of Internalization and Intracellular Trafficking","volume":"22","author":"Monnery","year":"2021","journal-title":"Biomacromolecules"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"105032","DOI":"10.1016\/j.chemphyslip.2020.105032","article-title":"Cationic lipids for gene delivery: Many players, one goal","volume":"235","author":"Ponti","year":"2021","journal-title":"Chem. Phys. Lipids"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1007\/s00253-020-11028-6","article-title":"Progress of cationic gene delivery reagents for non-viral vector","volume":"105","author":"Ma","year":"2021","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1038\/s41573-024-00977-6","article-title":"The 60-year evolution of lipid nanoparticles for nucleic acid delivery","volume":"23","author":"Cullis","year":"2024","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Wysocka, M., Gruba, N., Grzywa, R., Gie\u0142do\u0144, A., B\u0105chor, R., Brzozowski, K., Sie\u0144czyk, M., Dieter, J., Szewczuk, Z., and Rolka, K. (2016). PEGylated substrates of NSP4 protease: A tool to study protease specificity. Sci. Rep., 6.","DOI":"10.1038\/srep22856"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2396","DOI":"10.3390\/ijms21072396","article-title":"A Peptidomimetic Fluorescent Probe to Detect the Trypsin beta2 Subunit of the Human 20S Proteasome","volume":"21","author":"Wysocka","year":"2020","journal-title":"Int. J. Mol. Sci."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Romanowska, A., W\u0119grzyn, K., Bury, K., Sikorska, E., Gnatek, A., Piwkowska, A., Konieczny, I., Lesner, A., and Wysocka, M. (2021). Novel Cell Permeable Polymers of N-Substituted L-2,3-Diaminopropionic Acid (DAPEGs) and Cellular Consequences of Their Interactions with Nucleic Acids. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22052571"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Romanowska, A., Rachubik, P., Piwkowska, A., and Wysocka, M. (2024). Polymers of functionalized diaminopropionic acid are efficient mediators of active exogenous enzyme delivery into cells. Sci. Rep., 14.","DOI":"10.1038\/s41598-024-64187-1"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Abaandou, L., Quan, D., and Shiloach, J. (2021). Affecting HEK293 Cell Growth and Production Performance by Modifying the Expression of Specific Genes. Cells, 10.","DOI":"10.3390\/cells10071667"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1016\/j.ijpharm.2015.09.006","article-title":"Fatty acid modified octa-arginine for delivery of siRNA","volume":"495","author":"Li","year":"2015","journal-title":"Int. J. Pharm."},{"key":"ref_15","first-page":"3271","article-title":"Delivery of siRNA Using Cationic Liposomes Incorporating Stearic Acid-modified Octa-Arginine","volume":"36","author":"Yang","year":"2016","journal-title":"Anticancer Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/j.jconrel.2018.02.016","article-title":"Synergism between a cell penetrating peptide and a pH-sensitive cationic lipid in efficient gene delivery based on double-coated nanoparticles","volume":"275","author":"Khalil","year":"2018","journal-title":"J. Control. Release"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1005","DOI":"10.1021\/bc015508l","article-title":"Stearylated arginine-rich peptides: A new class of transfection systems","volume":"12","author":"Futaki","year":"2001","journal-title":"Bioconjugate Chem."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"5284","DOI":"10.1093\/nar\/gkr072","article-title":"PepFect 14, a novel cell-penetrating peptide for oligonucleotide delivery in solution and as solid formulation","volume":"39","author":"Ezzat","year":"2011","journal-title":"Nucleic Acids Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"782","DOI":"10.1021\/acs.bioconjchem.6b00680","article-title":"Saturated Fatty Acid Analogues of Cell-Penetrating Peptide PepFect14: Role of Fatty Acid Modification in Complexation and Delivery of Splice-Correcting Oligonucleotides","volume":"28","author":"Lehto","year":"2017","journal-title":"Bioconjugate Chem."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/30\/7\/1644\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:11:50Z","timestamp":1760029910000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/30\/7\/1644"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,7]]},"references-count":19,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2025,4]]}},"alternative-id":["molecules30071644"],"URL":"https:\/\/doi.org\/10.3390\/molecules30071644","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4,7]]}}}