Evaluating TNA stability under simulated physiological conditions

Michelle C. Culbertson, Kartik Temburnikar, Sujay P. Sau, Jen Yu Liao, Saikat Bala, John C. Chaput

Research output: Contribution to journalArticle

Abstract

Chemically modified oligonucleotides are routinely used as diagnostic and therapeutic agents due to their enhanced biological stability relative to natural DNA and RNA. Here, we examine the biological stability of α-l-threofuranosyl nucleic acid (TNA), an artificial genetic polymer composed of repeating units of α-l-threofuranosyl sugars linked by 2′,3′-phosphodiester bonds. We show that TNA remains undigested after 7 days of incubation in the presence of either 50% human serum or human liver microsomes and is stable against snake venom phosphordiesterase (a highly active 3′ exonuclease). We further show that TNA will protect internal DNA residues from nuclease digestion and shield complementary RNA strands from RNA degrading enzymes. Together, these results demonstrate that TNA is an RNA analogue with high biological stability.

Original languageEnglish (US)
Pages (from-to)2418-2421
Number of pages4
JournalBioorganic and Medicinal Chemistry Letters
Volume26
Issue number10
DOIs
StatePublished - May 1 2016
Externally publishedYes

Fingerprint

Nucleic Acids
spleen exonuclease
RNA
Complementary RNA
Snake Venoms
Deoxyribonucleases
DNA
Liver Microsomes
Oligonucleotides
Sugars
Liver
Digestion
Polymers
Enzymes
Serum
Therapeutics

Keywords

  • Biological stability
  • RNA analogue
  • Threose nucleic acid

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

Cite this

Evaluating TNA stability under simulated physiological conditions. / Culbertson, Michelle C.; Temburnikar, Kartik; Sau, Sujay P.; Liao, Jen Yu; Bala, Saikat; Chaput, John C.

In: Bioorganic and Medicinal Chemistry Letters, Vol. 26, No. 10, 01.05.2016, p. 2418-2421.

Research output: Contribution to journalArticle

Culbertson, Michelle C. ; Temburnikar, Kartik ; Sau, Sujay P. ; Liao, Jen Yu ; Bala, Saikat ; Chaput, John C. / Evaluating TNA stability under simulated physiological conditions. In: Bioorganic and Medicinal Chemistry Letters. 2016 ; Vol. 26, No. 10. pp. 2418-2421.
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