title: Lipitoids--novel cationic lipids for cellular delivery of plasmid DNA in vitro.
abstract: 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.
authors.affiliation: Chiron Technologies, Chiron Corporation, Emeryville, CA 94608, USA.
authors.forename: C Y
authors.initials: CY
authors.lastname: Huang
authors.forename: T
authors.initials: T
authors.lastname: Uno
authors.forename: J E
authors.initials: JE
authors.lastname: Murphy
authors.forename: S
authors.initials: S
authors.lastname: Lee
authors.forename: J D
authors.initials: JD
authors.lastname: Hamer
authors.forename: J A
authors.initials: JA
authors.lastname: Escobedo
authors.forename: F E
authors.initials: FE
authors.lastname: Cohen
authors.forename: R
authors.initials: R
authors.lastname: Radhakrishnan
authors.forename: V
authors.initials: V
authors.lastname: Dwarki
authors.forename: R N
authors.initials: RN
authors.lastname: Zuckermann
mesh_terms: D016475:3T3 Cells; D000818:Animals; D019556:COS Cells; D002412:Cations / Q000138:chemical synthesis / Q000633:toxicity; D004247:DNA / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D003850:Deoxyribonuclease I / Q000378:metabolism; D004337:Drug Carriers / Q000138:chemical synthesis / Q000633:toxicity; D004587:Electrophoresis, Agar Gel; D005354:Fibrosarcoma; D006801:Humans; D046911:Macromolecular Substances; D051379:Mice; D008854:Microscopy, Electron; D010316:Particle Size; D034444:Peptoids; D010743:Phospholipids / Q000138:chemical synthesis* / Q000633:toxicity; D010957:Plasmids / Q000187:drug effects / Q000378:metabolism*; D013499:Surface Properties; D014162:Transfection / Q000379:methods
chemical_list: D002412:Cations; D004337:Drug Carriers; D046911:Macromolecular Substances; D034444:Peptoids; D010743:Phospholipids; D004247:DNA; D003850:Deoxyribonuclease I