Locked nucleic acid

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.

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

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

Synthesis

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

Therapeutic applications

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
  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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