Document Detail


Structure-editing of nucleic acids for selective targeting of RNA.
MedLine Citation:
PMID:  17430211     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The synthesis of backbone-modified nucleic acids has been an area of very intense research over the last two decades. The main reason for this research activity is the instability of nucleic acid based drugs in the intracellular conditions. Changes in the sugar-phosphate backbone invariably bring about the changes in the complementation properties of the nucleic acids. The naturally occurring deoxyribose- (DNA) and ribose (RNA) sugar-phosphate backbones are endowed with considerable differences in their binding affinities towards themselves. This occurs because of the different sugar conformations prevalent in DNA and RNA and the subtle structural changes accruing from these in hydrogen bonding, base-stacking interactions and hydration of major/minor grooves. The six-atom phosphodiester linkages and pentose-sugars give immense opportunities for chemical modifications that lead to several backbone-modified nucleic acid structures. This article is focused on such modifications that impart RNA-selective binding properties to the modified nucleic acid mimics and the rationale behind the said selectivity. It is found that the six-atom sugar-phosphate backbone could be replaced by either one-atom extended or one-atom edited repeating units, leading to the folded or extended geometries to maintain the internucleoside distance-complementarity. Other important contributions come from electronegativity of the substituent groups, hydration in the major/minor groove, base stacking etc.
Authors:
Vaijayanti A Kumar; K N Ganesh
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Review    
Journal Detail:
Title:  Current topics in medicinal chemistry     Volume:  7     ISSN:  1873-4294     ISO Abbreviation:  Curr Top Med Chem     Publication Date:  2007  
Date Detail:
Created Date:  2007-04-13     Completed Date:  2007-05-29     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101119673     Medline TA:  Curr Top Med Chem     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  715-26     Citation Subset:  IM    
Affiliation:
Division of Organic Chemistry, Synthesis, National Chemical Laboratory, Pune, 411008 India. va.kumar@ncl.res.in
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MeSH Terms
Descriptor/Qualifier:
Amines / chemistry
Animals
Biomimetic Materials / chemistry
Humans
Nucleic Acid Conformation
Nucleic Acids / chemistry*
Phosphorus / chemistry
RNA / chemistry*
Stereoisomerism
Substrate Specificity
Sulfhydryl Compounds / chemistry
Chemical
Reg. No./Substance:
0/Amines; 0/Nucleic Acids; 0/Sulfhydryl Compounds; 63231-63-0/RNA; 7723-14-0/Phosphorus

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