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

[Image: see text] 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′-...

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Autores principales: Varada, Manojkumar, Aher, Manisha, Erande, Namrata, Kumar, Vaijayanti A., Fernandes, Moneesha
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2019
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6964305/
https://www.ncbi.nlm.nih.gov/pubmed/31956796
http://dx.doi.org/10.1021/acsomega.9b03042
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author Varada, Manojkumar
Aher, Manisha
Erande, Namrata
Kumar, Vaijayanti A.
Fernandes, Moneesha
author_facet Varada, Manojkumar
Aher, Manisha
Erande, Namrata
Kumar, Vaijayanti A.
Fernandes, Moneesha
author_sort Varada, Manojkumar
collection PubMed
description [Image: see text] 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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spelling pubmed-69643052020-01-17 Methoxymethyl Threofuranosyl Thymidine (4′-MOM-TNA-T) at the T7 Position of the Thrombin-Binding Aptamer Boosts Anticoagulation Activity, Thermal Stability, and Nuclease Resistance Varada, Manojkumar Aher, Manisha Erande, Namrata Kumar, Vaijayanti A. Fernandes, Moneesha ACS Omega [Image: see text] 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. American Chemical Society 2019-12-26 /pmc/articles/PMC6964305/ /pubmed/31956796 http://dx.doi.org/10.1021/acsomega.9b03042 Text en Copyright © 2019 American Chemical Society This is an open access article published under an ACS AuthorChoice License (http://pubs.acs.org/page/policy/authorchoice_termsofuse.html) , which permits copying and redistribution of the article or any adaptations for non-commercial purposes.
spellingShingle Varada, Manojkumar
Aher, Manisha
Erande, Namrata
Kumar, Vaijayanti A.
Fernandes, Moneesha
Methoxymethyl Threofuranosyl Thymidine (4′-MOM-TNA-T) at the T7 Position of the Thrombin-Binding Aptamer Boosts Anticoagulation Activity, Thermal Stability, and Nuclease Resistance
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
title_full Methoxymethyl Threofuranosyl Thymidine (4′-MOM-TNA-T) at the T7 Position of the Thrombin-Binding Aptamer Boosts Anticoagulation Activity, Thermal Stability, and Nuclease Resistance
title_fullStr Methoxymethyl Threofuranosyl Thymidine (4′-MOM-TNA-T) at the T7 Position of the Thrombin-Binding Aptamer Boosts Anticoagulation Activity, Thermal Stability, and Nuclease Resistance
title_full_unstemmed Methoxymethyl Threofuranosyl Thymidine (4′-MOM-TNA-T) at the T7 Position of the Thrombin-Binding Aptamer Boosts Anticoagulation Activity, Thermal Stability, and Nuclease Resistance
title_short Methoxymethyl Threofuranosyl Thymidine (4′-MOM-TNA-T) at the T7 Position of the Thrombin-Binding Aptamer Boosts Anticoagulation Activity, Thermal Stability, and Nuclease Resistance
title_sort methoxymethyl threofuranosyl thymidine (4′-mom-tna-t) at the t7 position of the thrombin-binding aptamer boosts anticoagulation activity, thermal stability, and nuclease resistance
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6964305/
https://www.ncbi.nlm.nih.gov/pubmed/31956796
http://dx.doi.org/10.1021/acsomega.9b03042
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