Versatile Method to Link Diagnostics and/or Therapeutics to Biomolecules
The site-directed modification of e.g. biomolecules is often time consuming and laborious. This invention provides a high yielding and highly specific method to link nearly any molecule to nearly any other molecule. The “Click reaction” used is the well known Diels-Alder reaction with inverse electron
The “Click reaction” used is the well known DielsAlder reaction with inverse electron demand (DARinv). In this fast reaction an appropriate, easily functionalized dien (e.g. Tetrazin 1) is reacted with an appropriate functionalized dienophil (e.g. Olefin 2) to yield the product 3. The release of nitrogen 4 makes the reaction irreversible. No side reactions occur (Scheme). Transient protection of functional groups of the molecules to be linked with this method is obsolete. Further no activation of the reacting compounds is necessary and thus there are no restrictions to the solvents to be used for the reaction, i.e. organic solvents, alcohols and even water are appropriate solvents. The invention discloses several applications for this reaction:
- ligation of diagnostics or therapeutics to peptides, oligo nucleotides or saccharides
- Modification of surfaces and solid phases
- Preparation of dendritic structures and quantum dots
Further the Intellectual Property covers specific information regarding the combination of above mentioned applications e.g. the ligation of a diagnostic marker AND a therapeutic agent AND a biomolecule.
Bilder & Videos
- Simple synthetic pathways
- Versatile starting materials
- High yielding, easy to monitor reactions without side reactions
- Re-formulation of “old fashioned” drugs & diagnostics
- Applicable to surface modifications
- Improvement of production processes (higher yield) in particular for biomolecules.
- Chip production: DNA, Protein or Carbon hydrate (i.e. Saccharide) Chips
DKFZ is currently seeking a commercial partner to develop this technology under an exclusive licence and/or collaboration agreement. Exclusive licensing for specific applications/indications is possible.
Publikationen & Verweise
- “The Diels-Alder-reaction with inverseelectron-demand, a very efficient versatile click-reaction concept for proper ligation of variable molecular partners.” Wiessler M, Waldeck W, Kliem C, Pipkorn R, Braun K. in Int J Med Sci. 2009 Dec 5;7(1):19-28. See: https://www.ncbi.nlm.nih.gov/pubmed/?term=20046231
- “Treatment of glioblastoma multiforme cells with temozolomide-BioShuttle ligated by the inverse Diels-Alder ligation chemistry.” Braun K, Wiessler M, Ehemann V, Pipkorn R, Spring H, Debus J, Didinger B, Koch M, Muller G, Waldeck W. in Drug Des Devel Ther. 2009 Feb 6;2:289-301. See: https://www.ncbi.nlm.nih.gov/pubmed/?term=19920915
- Inverse-electron-demand Diels-Alder reaction as a highly efficient chemoselective ligation procedure: synthesis and function of a BioShuttle for temozolomide transport into prostate cancer cells. Pipkorn R, Waldeck W, Didinger B, Koch M, Mueller G, Wiessler M, Braun K. in J Pept Sci. 2009 Mar;15(3):235-41. See: https://www.ncbi.nlm.nih.gov/pubmed/?term=19177421
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