| Bioorg. Chem.
| Local Info
Research concerning Isotope Labelled Nucleic Acids
A New Isotope Labeling Technology for Licensing !
The New Concept of "NMR-window" Created by the Deuteration Technique for the
Determination of the Biological Structure of Large DNA or RNA
The RNA and DNA molecules that are amenable to conformational studies by the
state-of-the-art 600/750 MHz NMR spectroscopy today are not larger than 12-14
mer in size owing to the severe overlap of resonances. Such short structures do
not represent true biological models, which should enable us to understand how
macromolecular structure and dynamics produce interaction and recognition that
translate into biological function! We have developed a deuterium-labeling
technique that should make it possible to tackle the structure of larger DNA
and RNA molecules of the size of a gene (~100 nucleotides or larger) or of a
functional tRNA (~75 nucleotide residues). The powerful combination of the
proposed partial deuteration techniques and NMR spectroscopy provide unique
opportunities and scope to both chemists and biophysicists for the structural
determination of larger functional biomolecules by standard multidimensional
- All eight deuterated nucleoside blocks for RNA and DNA synthesis have now
been prepared by us in 96-97 atom % D purity in a stereospecific manner
on a large scale by chemical methodologies. A provisional patent has been filed,
and we are looking forward to collaboration with a business partner prepared
to develop the isotope labeling strategies for the NMR work, and the
marketing of the isotope-labeled products for structural studies of
- A solid phase synthetic approach for DNA or RNA synthesis combining these
deuterated blocks in conjunction with natural nucleosides gives a partially
deuterated molecule which is specifically deuterated at certain specific
parts and non-deuterated elsewhere in the molecule, thus creating the
See our publications:
These publications clearly show the merits of our deuteration approach.
It reduces overlap of resonances in NMR spectra, thereby allowing structural
investigation of much larger molecules of DNA and RNA than is possible
today, using the state-of-the-art NMR techniques.
- Tetrahedron, 48, 9033 (1992)
- J. Biochemical & Biophysical Methods, 26, 2287 (1993)
- Nucleic Acids Res, 21, 5005 (1994)
- Nucleic Acids Res, 22, 1404 (1994)
- Tetrahedron, 51, 10065 (1995)
Contact Prof. J. Chattopadhyaya for further information:
- Department of Bioorganic Chemistry, Box 581, Biomedical Centre,
Uppsala University, S-751 23 Uppsala, Sweden.
Tel: +46-18-4714577; Fax: +46-18-554495.
Dep't of Bioorg. Chem.
| Last mod.: Nov 6, 2002
| URL http://www.boc.uu.se/
| WWW Editor