Novel Method for Reverse Automated Nucleic Acid Synthesis

Description:

Project ID:  D2017-49

 

Background

Automated processes are widely used in the synthesis of modified oligonucleotide strands.  These modified oligonucleotides are useful in the treatment or investigation of various conditions and diseases. Currently, the most common subunits used to synthesize RNA strands in the 3 to 5 direction are 3 phosphoramidites. There remains a need for novel methods to facilitate RNA synthesis form the 5 to 3 position using H-phosphonate chemistry.

 

Invention Description

Researchers at the University of Toledo, led by Dr. Amanda Bryant-Friedrich, have developed a novel automated method to synthesize oligonucleotides, which reduces the number of required steps and also allows for more flexibility in in adding modifications to the sugar moiety. The method developed here relies novel activated monomers for polymer synthesis and takes advantage of existing standard protocols and reagents, which will allow easy integration into conventional protocols. This process that employs 5 H-phosphonate modified ribonucleotides to allow for the automated synthesis of modified RNA in the 5 to 3 direction. 

 

Applications

•       Tools for the investigation of biological processes

•       Synthesis of artificial genes

•       Antisense small oligonucleotides (snRNA)

 

Advantages

•       The monomers and solid supports used in the synthesis are novel and unavailable commercially

•       The synthesis procedure uses less steps and is more economical than conventional methods

•       The synthesis method used results in enhanced chemical stability of the monomers

•       The method is amenable to the inclusion of sugar modifications

•       The synthesis method developed here is more environmentally friendly and based on well-established polymer synthesis chemistry

•       The method developed takes advantage of conventional protocols and reagents and can be easily incorporated into currently existing protocols for oligonucleotide synthesis

 

IP Status:       Patent Pending

 

Publications:       

Bedi MF et al., Synthesis of damaged DNA containing the oxidative lesion 3’-oxothymidine. Bioorganic Medicinal Chemistry, 2017, 5598-5602

 

       Audat SA et al., Synthesis of C3’ modified nucleosides for selective generation of the C3’-deoxy-3’-thymidinyl radical: a proposed intermediate in LEE induced               DNA damage. Journal of Organic Chemistry, 2012, 3829-3837

 

Patent Information:
Category(s):
Polymers
Research Tools
For Information, Contact:
Kwaku Opoku
Licensing Associate
The University of Toledo
419-530-6231
kwaku.opoku@utoledo.edu
Inventors:
Amanda Bryant-Friedrich
Matthew Ellis
Keywords:
DNA
Nucleic acid
Oligomer
Oligonucleotide
Phosphonate
RNA
Synthesis