The size of the internal loop in DNA hairpins influences their targeting with partially complementary strands

Iztok Prislan, Hui Ting Lee, Cynthia Lee, Luis A Marky

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Targeting of noncanonical DNA structures, such as hairpin loops, may have significant diagnostic and therapeutic potential. Oligonucleotides can be used for binding to mRNA, forming a DNA/RNA hybrid duplex that inhibits translation. This kind of modulation of gene expression is called the antisense approach. In order to determine the best strategy to target a common structural motif in mRNA, we have designed a set of stem-loop DNA molecules with sequence: d(GCGCTnGTAAT5GTTACTnGCGC), where n = 1, 3, or 5, "T5" is an end loop of five thymines. We used a combination of calorimetric and spectroscopy techniques to determine the thermodynamics for the reaction of a set of hairpins containing internal loops with their respective partially complementary strands. Our aim was to determine if internal- and end-loops are promising regions for targeting with their corresponding complementary strands. Indeed, all targeting reactions were accompanied by negative changes in free energy, indicating that reactions proceed spontaneously. Further investigation showed that these negative free energy terms result from a net balance of unfavorable entropy and favorable enthalpy contributions. In particular, unfolding of hairpins and duplexes is accompanied by positive changes in heat capacity, which may be a result of exposure of hydrophobic groups to the solvent. This study provides a new method for the targeting of mRNA in order to control gene expression. (Figure Presented).

Original languageEnglish (US)
Pages (from-to)96-104
Number of pages9
JournalJournal of Physical Chemistry B
Volume119
Issue number1
DOIs
StatePublished - Jan 8 2015

Fingerprint

strands
DNA
deoxyribonucleic acid
Gene expression
Messenger RNA
Free energy
gene expression
Thymine
Oligonucleotides
RNA
Specific heat
free energy
Enthalpy
Entropy
Modulation
Spectroscopy
Thermodynamics
thymine
oligonucleotides
Molecules

ASJC Scopus subject areas

  • Surfaces, Coatings and Films
  • Physical and Theoretical Chemistry
  • Materials Chemistry

Cite this

The size of the internal loop in DNA hairpins influences their targeting with partially complementary strands. / Prislan, Iztok; Lee, Hui Ting; Lee, Cynthia; Marky, Luis A.

In: Journal of Physical Chemistry B, Vol. 119, No. 1, 08.01.2015, p. 96-104.

Research output: Contribution to journalArticle

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