Lipitoids--novel cationic lipids for cellular delivery of plasmid DNA in vitro

Chem Biol. 1998 Jun;5(6):345-54. doi: 10.1016/s1074-5521(98)90173-9.


Background: Although synthetic nonviral vectors hold promise for the delivery of plasmid DNA, their gene-transfer efficiencies are far from matching those of viruses. To systematically investigate the structure-activity relationship of cationic lipids, a small library of cationic lipid-peptoid conjugates (lipitoids) was synthesized. The compounds were evaluated for their ability to form complexes with plasmid DNA and to mediate DNA transfer in vitro.

Results: Lipid-peptoid conjugates were conveniently prepared in high yield using solid-phase synthesis. Several lipitoids condensed plasmid DNA into 100 nm spherical particles and protected the DNA and DNase digestion. A subset of lipitoids with a repeated (aminoethyl, neutral, neutral) sidechain trimer motif conjugated with dimyristoyl phosphatidyl-ethanolamine (DMPE) mediated DNA transfer with high efficiency.

Conclusions: Automated solid-phase synthesis of cationic lipids allowed the rapid synthesis of a diverse set of transfection reagents. The most active compound DMPE-(Nae-Nmpe-Nmpe)3 (Nae, N-aminoethyl glycine; Nmpe, N-p-methoxyphenethyl-glycine) is more efficient than lipofectin or DMRIE-C (two commercial cationic lipid transfection reagents) and is active in the presence and absence of serum. The activity in the presence of serum suggests potential for applications in vivo.

MeSH terms

  • 3T3 Cells
  • Animals
  • COS Cells
  • Cations / chemical synthesis
  • Cations / toxicity
  • DNA / drug effects
  • DNA / metabolism*
  • DNA / ultrastructure
  • Deoxyribonuclease I / metabolism
  • Drug Carriers / chemical synthesis
  • Drug Carriers / toxicity
  • Electrophoresis, Agar Gel
  • Fibrosarcoma
  • Humans
  • Macromolecular Substances
  • Mice
  • Microscopy, Electron
  • Particle Size
  • Peptoids
  • Phospholipids / chemical synthesis*
  • Phospholipids / toxicity
  • Plasmids / drug effects
  • Plasmids / metabolism*
  • Surface Properties
  • Transfection / methods


  • Cations
  • Drug Carriers
  • Macromolecular Substances
  • Peptoids
  • Phospholipids
  • DNA
  • Deoxyribonuclease I