A novel cell‐penetrating lipopeptide for DNA binding, self‐assembly, and delivery Into HeLa and Pluripotent stem cells

de Mello, L. R., Honda, T. S. B., Castelletto, V. ORCID: https://orcid.org/0000-0002-3705-0162, Alves, P. T., Han, S. W., da Silva, E. R. ORCID: https://orcid.org/0000-0001-5876-2276 and Hamley, I. W. ORCID: https://orcid.org/0000-0002-4549-0926 (2026) A novel cell‐penetrating lipopeptide for DNA binding, self‐assembly, and delivery Into HeLa and Pluripotent stem cells. Journal of Peptide Science, 32 (3). e70085. ISSN 1099-1387 doi: 10.1002/psc.70085

Abstract/Summary

A lipopeptide is designed that contains an epitope from simian virus T‐antigen (SV40T, PKKKRKV) conjugated to an N‐terminal palmitoyl (C 16 ‐) moiety, with the aim to act as an effective cell‐penetrating lipopeptide, with additional aggregation propensity conferred by the lipid chain. A combination of cryo‐TEM and small‐angle X‐ray scattering (SAXS) is used to show that the lipopeptide forms micelles, but mixtures with DNA lead to formation of fractal cluster‐like co‐assemblies due to intercalation of the DNA and peptide. Spectroscopic studies using fluorescence and circular dichroism (along with fiber X‐ray diffraction) show that the peptide interacts with DNA and inserts into the groove. Confocal microscopy along with flow cytometry confirms delivery of DNA into both HeLa and mouse embryonic stem cells (mESCs) in pluripotent state, and the system shows excellent cytocompatibility as confirmed by MTT assays. Our data indicate that the lipopeptide may outperform the DNA transfection agent lipofectamine in DNA delivery into these stem cells and it enables DNA delivery into the cytoplasm and nucleus.

Item Type	Article
URI	https://centaur.reading.ac.uk/id/eprint/128233
Identification Number/DOI	10.1002/psc.70085
Refereed	Yes
Divisions	Life Sciences > School of Chemistry, Food and Pharmacy > Department of Chemistry
Publisher	Wiley
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