A chemical synthesis of LNA-2,6-diaminopurine riboside, and the influence of 2′-O-2,6-diaminopurine and LNA-2,6-diaminopurine ribosides on the thermodynamic properties of 2′O-methyl RNA/RNA heteroduplexes

Institute of Bioorganic Chemistry, Polish Academy of Sciences, 60-714 Poznan, Noskowskiego 12/14, Poland.
Nucleic Acids Research (Impact Factor: 9.11). 02/2007; 35(12):4055-63. DOI: 10.1093/nar/gkm421
Source: PubMed


Modified nucleotides are useful tools to study the structures, biological functions and chemical and thermodynamic stabilities
of nucleic acids. Derivatives of 2,6-diaminopurine riboside (D) are one type of modified nucleotide. The presence of an additional
amino group at position 2 relative to adenine results in formation of a third hydrogen bond when interacting with uridine.
New method for chemical synthesis of protected 3′-O-phosphoramidite of LNA-2,6-diaminopurine riboside is described. The derivatives of 2′-O-methyl-2,6-diaminopurine and LNA-2,6-diaminopurine ribosides were used to prepare complete 2′-O-methyl RNA and LNA-2′-O-methyl RNA chimeric oligonucleotides to pair with RNA oligonucleotides. Thermodynamic stabilities of these duplexes demonstrated
that replacement of a single internal 2′-O-methyladenosine with 2′-O-methyl-2,6-diaminopurine riboside (DM) or LNA-2,6-diaminopurine riboside (DL) increases the thermodynamic stability (ΔΔG°37) on average by 0.9 and 2.3 kcal/mol, respectively. Moreover, the results fit a nearest neighbor model for predicting duplex
stability at 37°C. D-A and D-G but not D-C mismatches formed by DM or DL generally destabilize 2′-O-methyl RNA/RNA and LNA-2′-O-methyl RNA/RNA duplexes relative to the same type of mismatches formed by 2′-O-methyladenosine and LNA-adenosine, respectively. The enhanced thermodynamic stability of fully complementary duplexes and
decreased thermodynamic stability of some mismatched duplexes are useful for many RNA studies, including those involving microarrays.

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Available from: Anna Pasternak, Apr 01, 2014
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    • "PK, HP, and HPMut were hybridized to microarrays with 861 chimeric pentamer and hexamer oligonucleotides containing 2′-O-methyl RNAs with locked nucleic acid (LNA) and 2,6-diaminopurine modifications at selected positions to roughly equalize the thermodynamic stability of hybridization to unstructured RNA [37], [38], [39], [40]. Results for probes with five consecutive nucleotides Watson-Crick complementary to 3PSS are listed in Table S1. "
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