Nucleic acid technology has revolutionized the field of biomedicine, as it can be effectively utilized in the diagnosis, treatment, and prevention of genetic diseases.
The efficacy of most oligonucleotide therapies is, however, limited as a result of the lability of oligonucleotides in biological fluids and, in particular, their poor delivery to the site of action. A Swedish team headed by R. Strömberg recently reported in the European Journal of Organic Chemistry that modification of oligonucleotides with a 2'-O-carbamoyl moiety greatly increases the stability of these compounds, which may render their use in constructs for biotechnological and therapeutic applications viable.
Efficiency in the regulation of gene expression is readily achieved if turnover of the target RNA is obtained, but this can only occur if native enzymes recognize the relevant oligonucleotide complex. The ability to catalytically cleave a specific sequence of RNA at a specific site is of high potential value in biotechnology and oligonucleotide therapy. Thus, the development of oligonucleotide-based artificial nucleases (OBANs) as artificial enzymes capable of cleaving mRNA sequences arising from genetic or viral diseases is highly sought.
In this context, the scientists set out to modify oligonucleotides with the judicious choice of a 2'-carbamoylmethyl (CM) moiety. Substitution at the 2-position was an important prerequisite, as this has been shown to lead to the formation of stable duplexes with the target RNA, and it was also believed that the CM moiety could further increase the stability of the duplex through hydrogen bonding.
The team was able to show that the 2'-O-carbamoyl modification substantially protected the dinucleotide against enzyme-catalyzed degradation by phosphodiesterase I and made it virtually resistant to degradation by phosphodiesterase II. This, together with the reported increased thermal stability of the duplexes, makes the often-neglected 2'-O-carbamoyl moiety an interesting modification in the pursuit of future compounds that may one day help in the treatment of genetic diseases.Author: Roger Strömberg, Karolinska Institutet, Stockholm (Sweden), http://www.bionut.ki.se/groups/rst/
Roger Strömberg | Wiley-VCH
Bioenergy cropland expansion could be as bad for biodiversity as climate change
11.12.2018 | Senckenberg Forschungsinstitut und Naturmuseen
How glial cells develop in the brain from neural precursor cells
11.12.2018 | Universitätsmedizin der Johannes Gutenberg-Universität Mainz
Over the last decade, there has been much excitement about the discovery, recognised by the Nobel Prize in Physics only two years ago, that there are two types...
What if a sensor sensing a thing could be part of the thing itself? Rice University engineers believe they have a two-dimensional solution to do just that.
Rice engineers led by materials scientists Pulickel Ajayan and Jun Lou have developed a method to make atom-flat sensors that seamlessly integrate with devices...
Scientists at the University of Stuttgart and the Karlsruhe Institute of Technology (KIT) succeed in important further development on the way to quantum Computers.
Quantum computers one day should be able to solve certain computing problems much faster than a classical computer. One of the most promising approaches is...
New Project SNAPSTER: Novel luminescent materials by encapsulating phosphorescent metal clusters with organic liquid crystals
Nowadays energy conversion in lighting and optoelectronic devices requires the use of rare earth oxides.
Scientists have discovered the first synthetic material that becomes thicker - at the molecular level - as it is stretched.
Researchers led by Dr Devesh Mistry from the University of Leeds discovered a new non-porous material that has unique and inherent "auxetic" stretching...
10.12.2018 | Event News
06.12.2018 | Event News
03.12.2018 | Event News
11.12.2018 | Physics and Astronomy
11.12.2018 | Materials Sciences
11.12.2018 | Information Technology