title: A chemical synthesis of LNA-2,6-diaminopurine riboside, and the influence of 2'-O-methyl-2,6-diaminopurine and LNA-2,6-diaminopurine ribosides on the thermodynamic properties of 2'-O-methyl RNA/RNA heteroduplexes.
abstract: 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 (D(M)) or LNA-2,6-diaminopurine riboside (D(L)) increases the thermodynamic stability (DeltaDeltaG degrees 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 degrees C. D-A and D-G but not D-C mismatches formed by D(M) or D(L) 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.
authors.affiliation: Institute of Bioorganic Chemistry, Polish Academy of Sciences, 60-714 Poznan, Noskowskiego 12/14, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Pasternak
authors.forename: Elzbieta
authors.initials: E
authors.lastname: Kierzek
authors.forename: Karol
authors.initials: K
authors.lastname: Pasternak
authors.forename: Douglas H
authors.initials: DH
authors.lastname: Turner
authors.forename: Ryszard
authors.initials: R
authors.lastname: Kierzek
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D020137:Base Pair Mismatch; D009841:Oligonucleotides; D016376:Oligonucleotides, Antisense / Q000138:chemical synthesis / Q000737:chemistry*; D009843:Oligoribonucleotides / Q000138:chemical synthesis / Q000737:chemistry*; D012313:RNA / Q000737:chemistry; D013816:Thermodynamics
chemical_list: C521717:2'-O-methyl-2,6-diaminopurine riboside; C521716:LNA-5'-O-dimethoxytrityl-N2,N6-diacetyl-2,6-diaminopurine riboside-3'-O-phosphoramidite; D009841:Oligonucleotides; D016376:Oligonucleotides, Antisense; D009843:Oligoribonucleotides; C477371:locked nucleic acid; D012313:RNA; D000241:Adenosine