Methoxymethyl Threofuranosyl Thymidine (4′-MOM-TNA-T) at the T7 Position of the Thrombin-Binding Aptamer Boosts Anticoagulation Activity, Thermal Stability, and Nuclease Resistance | Zendy

Manojkumar Varada | Zendy; Manisha Aher | Zendy; Namrata Erande | Zendy; Vaijayanti A. Kumar | Zendy; Moneesha Fernandes | Zendy

Open Access

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(s) -

Manojkumar Varada,

Manisha Aher,

Namrata Erande,

Vaijayanti A. Kumar,

Moneesha Fernandes

Publication year - 2019

Publication title -

acs omega

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 0.779

H-Index - 40

ISSN - 2470-1343

DOI - 10.1021/acsomega.9b03042

Subject(s) - nuclease , aptamer , thrombin , chemistry , thymidine , thermal stability , dna , biochemistry , microbiology and biotechnology , biology , platelet , immunology , organic chemistry

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.

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