Systematic evaluation of biophysical and functional characteristics of selenomethylene-locked nucleic acid-mediated inhibition of miR-21

TitleSystematic evaluation of biophysical and functional characteristics of selenomethylene-locked nucleic acid-mediated inhibition of miR-21
Publication TypeJournal Article
Year of Publication2016
AuthorsNahar, S, Singh, A, Morihiro, K, Moai, Y, Kodama, T, Obika, S, Maiti, S
JournalBiochemistry
Volume55
Issue50
Pagination7023-7032
Date PublishedDEC
AbstractmiRNAs constitute an important layer of gene regulation mediated by sequence-specific targeting of mRNAs. Aberrant expression of miRNAs contributes to a host of pathological states. Promoting cancer, miR-21 is upregulated in variety of cancers and promotes tumor progresion by suppressing a network of tumor suppressor genes. Here we describe a novel class of bicyclic RNA analogues, selenomethylene-locked nucleic acid (SeLNA), that display high affinity, improved metabolic stability, and increased potency for miR-21 inhibition. The thermal stability (T-m) for duplexes was increased significantly with incorporation of SeLNA monomers as compared to that of the unmodified DNA RNA hybrid. A comprehensive thermodynamic profile obtained by isothermal titration calorimetry revealed a favorable increase in the enthalpy of hybridization for SeLNA containing DNA and target RNA heteroduplexes. SeLNA modifications displayed remarkable binding affinity for miR-21 target RNA with a K-a of
DOI10.1021/acs.biochem.6b00895
Type of Journal (Indian or Foreign)Foreign
Impact Factor (IF)2.876
Divison category: 
Organic Chemistry