A flexible method for the conjugation of aminooxy ligands to preformed complexes of nucleic acids and lipids

James G. Hecker, Gideon O. Berger, Keith A. Scarfo, Shaomin Zou, Michael H. Nantz

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Attachment of targeted ligands to nonviral DNA or RNA delivery systems is a promising strategy that seeks to overcome the poor target selectivity generally observed in systemic delivery applications. Several methods have been developed for the conjugation of ligands to lipids or polymers, however, direct conjugation of ligands onto lipid-or polymer-nucleic acid complexes is not as straightforward. Here, we examine an oximation approach to directly label a lipoplex formulation. Specifically, we report the synthesis of a cationic diketo lipid DMDK, and its use as a convenient ligation tool for attachment of aminooxy-functionalized reagents after its complexation with DNA. We demonstrate the feasibility of direct lipoplex labeling by attaching an aminooxy-functionalized fluorescent probe onto pre-formed plasmid DNA-DMDK lipoplexes (luciferase, GFP). The results reveal that DMDK protects DNA from degradation on exposure to either DNase or human cerebral spinal fluid, and that simple mixing of DMDK lipoplexes with the aminooxy probe labels the complexes without sacrificing transfection efficiency. The biocompatibility and selectivity of this method, as well as the ease of bioconjugation, make this labeling approach ideal for biological applications.

Original languageEnglish (US)
Pages (from-to)1356-1361
Number of pages6
JournalChemMedChem
Volume3
Issue number9
DOIs
StatePublished - Sep 15 2008
Externally publishedYes

Fingerprint

Nucleic Acids
Ligands
Lipids
DNA
Labeling
Labels
Polymers
Deoxyribonucleases
Complexation
Luciferases
Biocompatibility
Fluorescent Dyes
Transfection
Ligation
Plasmids
RNA
Degradation
Fluids

Keywords

  • Gene transfer
  • Keto-lipids
  • Labeling
  • Oximation
  • Targeting

ASJC Scopus subject areas

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

Cite this

A flexible method for the conjugation of aminooxy ligands to preformed complexes of nucleic acids and lipids. / Hecker, James G.; Berger, Gideon O.; Scarfo, Keith A.; Zou, Shaomin; Nantz, Michael H.

In: ChemMedChem, Vol. 3, No. 9, 15.09.2008, p. 1356-1361.

Research output: Contribution to journalArticle

Hecker, James G. ; Berger, Gideon O. ; Scarfo, Keith A. ; Zou, Shaomin ; Nantz, Michael H. / A flexible method for the conjugation of aminooxy ligands to preformed complexes of nucleic acids and lipids. In: ChemMedChem. 2008 ; Vol. 3, No. 9. pp. 1356-1361.
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