Properties of double-stranded oligonucleotides modified with lipophilic substituents

Brian M. Laing, Lisa Barrow-Laing, Maureen Harrington, Eric C. Long, Donald E. Bergstrom

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

We have synthesized a series of short, self-complementary oligonucleotide sequences modified at their 5′- and/or 3′- termini with a lipophilic dodecane (C12); these systems serve as models to assess the biophysical properties of double-stranded DNA (dsDNA) equipped with potentially stabilizing lipophilic substituents. Addition of C12 to the 5′-termini of self-complementary 10 nucleotide sequences increased their duplex melting temperatures (Tm) by ∼4-8 °C over their corresponding unmodified sequences. C12 functionalities added to both the 3′- and 5′-termini increased Tm values by ∼10-12 °C. The observed increases in Tm correlated with greater duplex stabilities as determined by the free energy values (ΔG) derived from Tm plots. There is a greater degree of stabilization when C12 is positioned with a C·G base pair at the termini, and the stabilizing effect of lipophilic groups far exceeds the effect seen in adding an additional base pair to both ends of DNA. Stable, short dsDNA sequences are of potential interest in the development of transcription factor decoy oligonucleotides as possible therapeutic agents and/or biological tools. These results suggest that the stability of short dsDNA sequences are improved by lipophilic substituents and can be used as the basis for the design of dsDNAs with improved biological stabilities and function under physiological conditions.

Original languageEnglish (US)
Pages (from-to)1537-1544
Number of pages8
JournalBioconjugate Chemistry
Volume21
Issue number8
DOIs
StatePublished - Aug 18 2010

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Biomedical Engineering
  • Pharmacology
  • Pharmaceutical Science
  • Organic Chemistry

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