Title
Methoxymethyl Threofuranosyl Thymidine (4′-MOM-TNA-T) at the T7 Position of the Thrombin-Binding Aptamer Boosts Anticoagulation Activity, Thermal Stability, and Nuclease Resistance
Author
Manojkumar Varada, Manisha Aher, Namrata Erande, Vaijayanti A. Kumar, Moneesha Fernandes
Year
2020
Journal
ACS Omega
Abstract
The synthesis of 4′-methoxymethyl threofuranosyl (4′-MOM-TNA) thymidine and derived oligomers of the G-rich thrombin-binding aptameric (TBA) sequence is reported. The G-quadruplex stability, anticoagulation activity, and the enzymatic stability of these oligomers bearing the 2′-3′-phosphodiester backbone as single substitutions in the loop regions are studied. Amongst all the oligomers, TBA-7T bearing the 4′-MOM-TNA unit at the T7 position formed a quadruplex with the highest thermal stability. It also resulted in enhanced anticlotting activity that allowed a one-third reduction in the dose, relative to TBA. Further, TBA-7T exhibited enhanced nuclease resistance properties to both endo- and exonucleases.
Instrument
J-815
Keywords
Circular dichroism, Chemical stability, G-quadruplex structure, Thermal stability, Thermodynamics, Organic chemistry, Biochemistry