Document Detail

Insights from crystal structures into the opposite effects on RNA affinity caused by the S- and R-6'-methyl backbone modifications of 3'-fluoro hexitol nucleic acid.
MedLine Citation:
PMID:  22229409     Owner:  NLM     Status:  MEDLINE    
Locked nucleic acid (LNA) analogues with 2',4'-bridged sugars show promise in antisense applications. S-5'-Me-LNA has high RNA affinity, and modified oligonucleotides show weakened immune stimulation in vivo. Conversely, an R-5'-methyl group dramatically lowers RNA affinity. To test the effects of S- and R-6'-methyl groups on 3'-fluoro hexitol nucleic acid (FHNA) stability, we synthesized S- and R-6'-Me-FHNA thymidine and incorporated them into oligo-2'-deoxynucleotides. As with LNA, S-6'-Me is stabilizing whereas R-6'-Me is destabilizing. Crystal structures of 6'-Me-FHNA-modified DNAs explain the divergent consequences for stability and suggest convergent origins of these effects by S- and R-6'-Me (FHNA) [-5'-Me (LNA and RNA)] substituents.
Pradeep S Pallan; Jinghua Yu; Charles R Allerson; Eric E Swayze; Punit Seth; Martin Egli
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2011-12-29
Journal Detail:
Title:  Biochemistry     Volume:  51     ISSN:  1520-4995     ISO Abbreviation:  Biochemistry     Publication Date:  2012 Jan 
Date Detail:
Created Date:  2012-01-10     Completed Date:  2012-03-08     Revised Date:  2014-09-16    
Medline Journal Info:
Nlm Unique ID:  0370623     Medline TA:  Biochemistry     Country:  United States    
Other Details:
Languages:  eng     Pagination:  7-9     Citation Subset:  IM    
Data Bank Information
Bank Name/Acc. No.:
PDB/3V06;  3V07
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MeSH Terms
Crystallography, X-Ray
Hexosediphosphates / chemistry
Nucleic Acid Conformation*
Nucleic Acid Heteroduplexes / chemistry*
Oligonucleotides, Antisense / chemistry
RNA / chemistry*
Structure-Activity Relationship
Sugar Alcohols / chemistry*
Grant Support
Reg. No./Substance:
0/Hexosediphosphates; 0/Nucleic Acid Heteroduplexes; 0/Oligonucleotides, Antisense; 0/Sugar Alcohols; 0/hexitol; 63231-63-0/RNA

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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