1202937-26-5Relevant articles and documents
Synthesis and biophysical properties of C5-functionalized LNA (locked nucleic acid)
Kumar, Pawan,?stergaard, Michael E.,Baral, Bharat,Anderson, Brooke A.,Guenther, Dale C.,Kaura, Mamta,Raible, Daniel J.,Sharma, Pawan K.,Hrdlicka, Patrick J.
, p. 5047 - 5061 (2014/06/23)
Oligonucleotides modified with conformationally restricted nucleotides such as locked nucleic acid (LNA) monomers are used extensively in molecular biology and medicinal chemistry to modulate gene expression at the RNA level. Major efforts have been devoted to the design of LNA derivatives that induce even higher binding affinity and specificity, greater enzymatic stability, and more desirable pharmacokinetic profiles. Most of this work has focused on modifications of LNAs oxymethylene bridge. Here, we describe an alternative approach for modulation of the properties of LNA: i.e., through functionalization of LNA nucleobases. Twelve structurally diverse C5-functionalized LNA uridine (U) phosphoramidites were synthesized and incorporated into oligodeoxyribonucleotides (ONs), which were then characterized with respect to thermal denaturation, enzymatic stability, and fluorescence properties. ONs modified with monomers that are conjugated to small alkynes display significantly improved target affinity, binding specificity, and protection against 3'-exonucleases relative to regular LNA. In contrast, ONs modified with monomers that are conjugated to bulky hydrophobic alkynes display lower target affinity yet much greater 3'-exonuclease resistance. ONs modified with C5-fluorophore-functionalized LNA-U monomers enable fluorescent discrimination of targets with single nucleotide polymorphisms (SNPs). In concert, these properties render C5-functionalized LNA as a promising class of building blocks for RNA-targeting applications and nucleic acid diagnostics.
NUCLEOBASE-FUNCTIONALIZED CONFORMATIONALLY RESTRICTED NUCLEOTIDES AND OLIGONUCLEOTIDES FOR TARGETING NUCLEIC ACIDS
-
Page/Page column 109, (2011/04/18)
Embodiments are disclosed herein that involve C5-functionalized nucleic acids, which can be used for detecting a target in a nucleic acid. Particular embodiments disclose methods for making these compounds, wherein the compounds can be formed by coupling of an intermediate with a linker. Certain embodiments disclose the use of these compounds for detecting single nucleotide polymorphisms, and for increasing the thermal affinity of nucleic acid complements as compared to unmodified nucleic acid complements. In addition, the disclosed compounds can decrease enzymatic degradation of nucleic acids.
Optimized DNA-targeting using triplex forming C5-alkynyl functionalized LNA
Sau, Sujay P.,Kumar, Pawan,Anderson, Brooke A.,stergaard, Michael E.,Lee, Deobald,Paszczynski, Andrzej,Sharma, Pawan K.,Hrdlicka, Patrick J.
supporting information; scheme or table, p. 6756 - 6758 (2010/03/25)
Triplex forming oligonucleotides (TFOs) modified with C5-alkynyl functionalized LNA (locked nucleic acid) monomers display extraordinary thermal affinity toward double stranded DNA targets, excellent discrimination of Hoogsteenmismatched targets, and high
