Hydrophobic oxime ethers: A versatile class of pDNA and siRNA transfection lipids

Souvik Biswas, Ralph J. Knipp, Laura E. Gordon, Seshagiri R. Nandula, Sven Ulrik Gorr, Geoffrey J. Clark, Michael H. Nantz

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

The manipulation of the cationic lipid structures to increase polynucleotide binding and delivery properties, while also minimizing associated cytotoxicity, has been a principal strategy for developing next-generation transfection agents. The polar (DNA binding) and hydrophobic domains of transfection lipids have been extensively studied; however, the linking domain comprising the substructure used to tether the polar and hydrophobic domains has attracted considerably less attention as an optimization variable. Here, we examine the use of an oxime ether as the linking domain. Hydrophobic oxime ethers were readily assembled via click chemistry by oximation of hydrophobic aldehydes using an aminooxy salt. A facile ligation reaction delivered the desired compounds with hydrophobic domain asymmetry. Using the MCF-7 breast cancer, H1792 lung cancer and PAR C10 salivary epithelial cell lines, our findings show that lipoplexes derived from oxime ether lipids transfect in the presence of serum at higher levels than commonly used liposome formulations, based on both luciferase and green fluorescent protein (GFP) assays. Given the biological compatibility of oxime ethers and their ease of formation, this functional group should find significant application as a linking domain in future designs of transfection vectors.

Original languageEnglish (US)
Pages (from-to)2063-2069
Number of pages7
JournalChemMedChem
Volume6
Issue number11
DOIs
StatePublished - Nov 4 2011
Externally publishedYes

Fingerprint

Oximes
Ethers
Small Interfering RNA
Transfection
Lipids
Ether
Lung Neoplasms
Click Chemistry
Polynucleotides
Cytotoxicity
Green Fluorescent Proteins
Luciferases
Aldehydes
Liposomes
Functional groups
Ligation
Assays
Salts
Epithelial Cells
Breast Neoplasms

Keywords

  • Aminooxy salts
  • Gene transfer
  • Nonviral vectors
  • Oximation
  • Transfection agents

ASJC Scopus subject areas

  • Pharmacology, Toxicology and Pharmaceutics(all)
  • Organic Chemistry
  • Molecular Medicine

Cite this

Biswas, S., Knipp, R. J., Gordon, L. E., Nandula, S. R., Gorr, S. U., Clark, G. J., & Nantz, M. H. (2011). Hydrophobic oxime ethers: A versatile class of pDNA and siRNA transfection lipids. ChemMedChem, 6(11), 2063-2069. https://doi.org/10.1002/cmdc.201100259

Hydrophobic oxime ethers : A versatile class of pDNA and siRNA transfection lipids. / Biswas, Souvik; Knipp, Ralph J.; Gordon, Laura E.; Nandula, Seshagiri R.; Gorr, Sven Ulrik; Clark, Geoffrey J.; Nantz, Michael H.

In: ChemMedChem, Vol. 6, No. 11, 04.11.2011, p. 2063-2069.

Research output: Contribution to journalArticle

Biswas, S, Knipp, RJ, Gordon, LE, Nandula, SR, Gorr, SU, Clark, GJ & Nantz, MH 2011, 'Hydrophobic oxime ethers: A versatile class of pDNA and siRNA transfection lipids', ChemMedChem, vol. 6, no. 11, pp. 2063-2069. https://doi.org/10.1002/cmdc.201100259
Biswas S, Knipp RJ, Gordon LE, Nandula SR, Gorr SU, Clark GJ et al. Hydrophobic oxime ethers: A versatile class of pDNA and siRNA transfection lipids. ChemMedChem. 2011 Nov 4;6(11):2063-2069. https://doi.org/10.1002/cmdc.201100259
Biswas, Souvik ; Knipp, Ralph J. ; Gordon, Laura E. ; Nandula, Seshagiri R. ; Gorr, Sven Ulrik ; Clark, Geoffrey J. ; Nantz, Michael H. / Hydrophobic oxime ethers : A versatile class of pDNA and siRNA transfection lipids. In: ChemMedChem. 2011 ; Vol. 6, No. 11. pp. 2063-2069.
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