Locked nucleic acid

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Chemical structure of an LNA monomer an additional bridge bonds the 2' oxygen and the 4' carbon of the pentose

A locked nucleic acid (LNA), often referred to as inaccessible RNA, is a modified RNA nucleotide in which the ribose moiety is modified with an extra bridge connecting the 2' oxygen and 4' carbon. The bridge "locks" the ribose in the 3'-endo (North) conformation, which is often found in the A-form duplexes. LNA nucleotides can be mixed with DNA or RNA residues in the oligonucleotide whenever desired and hybridize with DNA or RNA according to Watson-Crick base-pairing rules.

The locked ribose conformation enhances base stacking and backbone pre-organization. This significantly increases the hybridization properties (melting temperature) of oligonucleotides.[1][2]

Synthesis[edit]

Synthesis was first reported in 1997.[3] Such oligomers are synthesized chemically and are commercially available.

Therapeutic applications[edit]

Using LNA based oligonucleotides therapeutically is an emerging field in biotechnology.[4] Allele-specific PCR using LNA allows for the design of shorter primers, without compromising binding specificity.[5]

Conformational structure of an LNA monomer β-D configuration

References[edit]

  1. ^ Kaur H, Arora A, Wengel J, Maiti S (June 2006). "Thermodynamic, counterion, and hydration effects for the incorporation of locked nucleic acid nucleotides into DNA duplexes". Biochemistry. 45 (23): 7347–55. doi:10.1021/bi060307w. PMID 16752924.
  2. ^ Owczarzy R, You Y, Groth CL, Tataurov AV (November 2011). "Stability and mismatch discrimination of locked nucleic acid-DNA duplexes". Biochemistry. 50 (43): 9352–67. doi:10.1021/bi200904e. PMC 3201676. PMID 21928795.
  3. ^ Satoshi O; Daishu N; Yoshiyuki H; Ken-ichiro M; Yasuko I; Toshimasa I; Takeshi I (1997). "Synthesis of 2′-O,4′-C-methyleneuridine and -cytidine. Novel bicyclic nucleosides having a fixed C3'-endo sugar puckering". Tetrahedron Lett. 38 (50): 8735–8738. doi:10.1016/S0040-4039(97)10322-7.
  4. ^ Petersen M, Wengel J (February 2003). "LNA: a versatile tool for therapeutics and genomics". Trends in Biotechnology. 21 (2): 74–81. doi:10.1016/S0167-7799(02)00038-0. PMID 12573856.
  5. ^ Bonetta L (2005). "Prime time for real-time PCR". Nat. Methods. 2 (4): 305–312. doi:10.1038/nmeth0405-305.

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