TY - JOUR
T1 - Evaluating TNA stability under simulated physiological conditions
AU - Culbertson, Michelle C.
AU - Temburnikar, Kartik W.
AU - Sau, Sujay P.
AU - Liao, Jen Yu
AU - Bala, Saikat
AU - Chaput, John C.
N1 - Funding Information:
We would like to thank members of the Chaput laboratory for helpful comments and suggestions. This work was supported by the DARPA Folded Non-Natural Polymers with Biological Function Fold F(x) Program under award number N66001-14-2-4054 and by a grant from the United States National Science Foundation MCB 1607111 .
Publisher Copyright:
© 2016 Elsevier B.V. All rights reserved.
PY - 2016/5/1
Y1 - 2016/5/1
N2 - 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.
AB - 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.
KW - Biological stability
KW - RNA analogue
KW - Threose nucleic acid
UR - http://www.scopus.com/inward/record.url?scp=84978328153&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84978328153&partnerID=8YFLogxK
U2 - 10.1016/j.bmcl.2016.03.118
DO - 10.1016/j.bmcl.2016.03.118
M3 - Article
C2 - 27080186
AN - SCOPUS:84978328153
SN - 0960-894X
VL - 26
SP - 2418
EP - 2421
JO - Bioorganic and Medicinal Chemistry Letters
JF - Bioorganic and Medicinal Chemistry Letters
IS - 10
ER -