Glycol nucleic acid

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Comparison of skeletons of T residue of GNA (red) and natural T nucleotide in DNA (blue) GNA-T vs. natural DNA-T.png
Comparison of skeletons of T residue of GNA (red) and natural T nucleotide in DNA (blue)

Glycol nucleic acid (GNA), sometimes also referred to as glycerol nucleic acid, is a nucleic acid similar to DNA or RNA but differing in the composition of its sugar-phosphodiester backbone, using propylene glycol in place of ribose or deoxyribose. [1] GNA is chemically stable but not known to occur naturally. However, due to its simplicity, it might have played a role in the evolution of life.

Contents

The 2,3-dihydroxypropyl nucleoside analogues were first prepared by Ueda et al. (1971). Soon thereafter it was shown that phosphate-linked oligomers of the analogues do in fact exhibit hypochromicity in the presence of RNA and DNA in solution (Seita et al. 1972). The preparation of the polymers was later described by Cook et al. (1995, 1999) and Acevedo and Andrews (1996). However the ability of GNA-GNA self-pairing was first reported by Zhang and Meggers in 2005. [1] Crystal structures of a GNA duplexes were subsequently reported by Essen and Meggers. [2] [3]

DNA and RNA have a deoxyribose and ribose sugar backbone, respectively, whereas GNA's backbone is composed of repeating glycol units linked by phosphodiester bonds. The glycol unit has just three carbon atoms and still shows Watson–Crick base pairing. The Watson–Crick base pairing is much more stable in GNA than its natural counterparts DNA and RNA as it requires a high temperature to melt a duplex of GNA. It is possibly the simplest of the nucleic acids, making it a hypothetical precursor to RNA.

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Eric Meggers is a German chemist and professor of organic chemistry and chemical biology at the University of Marburg, Germany. His research currently focuses on the design of chiral catalysts for stereoselective synthesis.

Gapmers are short DNA antisense oligonucleotide structures with RNA-like segments on both sides of the sequence. These linear pieces of genetic information are designed to hybridize to a target piece of RNA and silence the gene through the induction of RNase H cleavage. Binding of the gapmer to the target has a higher affinity due to the modified RNA flanking regions, as well as resistance to degradation by nucleases. Gapmers are currently being developed as therapeutics for a variety of cancers, viruses, and other chronic genetic disorders.

References

  1. 1 2 Zhang L, Peritz A, Meggers E (March 2005). "A simple glycol nucleic acid". Journal of the American Chemical Society. 127 (12): 4174–5. doi:10.1021/ja042564z. PMID   15783191.
  2. Schlegel MK, Essen LO, Meggers E (July 2008). "Duplex structure of a minimal nucleic acid". Journal of the American Chemical Society. 130 (26): 8158–9. doi:10.1021/ja802788g. PMC   2816004 . PMID   18529005.
  3. Schlegel MK, Essen LO, Meggers E (February 2010). "Atomic resolution duplex structure of the simplified nucleic acid GNA". Chemical Communications. 46 (7): 1094–6. doi:10.1039/B916851F. PMID   20126724.

Further reading