Properties of Double-Stranded Oligonucleotides Modified with Lipophilic Substituents

Brian M. Laing, Purdue University - Main Campus
Lisa Barrow-Laing, Indiana University - Bloomington
Maureen Harrington, Indiana University - Bloomington
Eric C. Long, Indiana University - Purdue University Indianapolis
Donald E. Bergstrom, Birck Nanotechnology Center and Bindley Bioscience Center, Purdue University

Date of this Version


This document has been peer-reviewed.



We have synthesized a series of short, self-complementary oligonucleotide sequences modified at their 5'- and/or 3'- termini with a lipophilic dodecane (C 12); 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 (T,) by similar to 4-8 degrees C over their corresponding unmodified sequences. C12 functionalities added to both the 3'- and 5'-termini increased T-m values by similar to 10-12 degrees C. The observed increases in T-m correlated with greater duplex stabilities as determined by the free energy values (Delta G) derived from T-m 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.


Engineering | Nanoscience and Nanotechnology