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ChemTech Expertise

New Click Reagents for Tyrosine and Lipid Bioconjugation

Triazolinediones (TADs) are highly reactive reagents that can be used to form a covalent link to unsaturated lipids and to solvent-exposed tyrosine residues in proteins (and peptides). The TAD-bioconjugation reactions are click-like (high yield, very selective, no byproducts, no additives/catalysts) and are also characterized by an extremely fast reaction, allowing the modification of low-abundant proteins and lipid metabolites such as vitamin D-metabolites.

Technology Offer of Ghent University presenting this novel click reagents based on TAD

Trapping Ligand-Protein interactions at the cell-surface

Interactions between ligands, such as peptides or small molecules, and cell surface proteins, such as G-protein coupled receptors (GPCR), are crucial for numerous key processes in living organisms, making them attractive drug targets. The method-of-choice to observe the interaction between these receptors and their ligands is by the formation of a stable chemical bond between both binding partners (crosslinking). Traditionally used photocrosslinking moieties can give rise to a high background crosslinking and the obligatory use of harmful UV light can result in phototoxic effects when working in living cells.

Recently, a new crosslinking technology was developed at Ghent University based on the use of a furan moiety which needs primary oxidative activation to allow covalent bond formation with nucleophilic sites in its proximity. With the present technology, one can use furan crosslinking to obtain a covalent bond between a ligand and its native cell-surface receptor without the need of such an external oxidation step. When working in living cells, the furan moiety, present in the ligand or in the cell-surface receptor, will be oxidized spontaneously upon formation of the ligand-receptor complex, and by this a highly specific crosslink will be formed between both binding partners.

Technology Offer: Trapping Ligand-Protein interactions at the cell-surface

Novel click reaction for labeling and conjugation 

A novel methodology has been developed which transforms furan-modified peptides and proteins to fluorescent probes in a single operation in solution, thus enlarging the toolbox of bio-orthogonal conjugations. Furan-peptides bearing sensitive residues such as tryptophan, methionine and histidine as well as a cell-penetrating peptide were subjected to the newly developed oxidiation and labeling protocol. 

Read more  in our poster and publication : Singlet Oxygen-Induced Furan Oxidation for Site-Specific and Chemoselective Peptide Ligation

TCI  and Irish Biotech also promote Furan photo-oxidation based click methodology of Prof. Madder.

FURAN CROSSLINKING for peptides and proteins

A cross-link methodology was developed, inspired by furan toxicity. For this purpose, a toolbox of furan modified nucleosides and amino acids was synthesized for incorporation in DNA or proteins. Upon oxidation, cross-links are formed efficiently, selectively and in high yield between DNA, RNA and proteins. Labeling is also possible with this furan oxidation methodology. Read more about our patented technolgy.

Furan Crosslinking technology

We are seeking partners interested in selective crosslinking of peptides and proteins for the identification of Protein-Protein interactions (PPIs). When using Furan technology to study PPI further characterization of PPI interfaces potentially allows defining new drug targets and potential new modes of action.

Tech Offer on UGent proprietary Furan Technolgy to study Protein-Protein Interactions 

CROSSLINKING METHODOLOGY FOR OLIGONUCLEOTIDES

The UGent Madder research group developed a unique crosslinking methodology for oligonucleotides based on the incorporation of furan moieties as has been demonstrated in several papers and projects.

A synthetic oligonucleotide model to evaluate oxidation and cross-linking propensity of natural furan modified DNA. L.L.G. Carrette, A. Madder ChemBioChem 15(1) 103-107 (2014) 

Toxicity Inspired Cross-linking for Probing DNA-peptide Interactions. L.L.G. Carette, T. Morii, A. Madder, Bioconj. Chem. 24(12), 2008-2014 (2013)

Sequence specific furan based DNA crosslinking with visual light, J. Am. Chem. Soc., 134 (26), 10737-10740 (2012)

Unprecedented C-Selective Interstrand Cross-Linking through in Situ Oxidation of Furan-Modified Oligodeoxynucleotides. J. Am. Chem. Soc. 133, 796-807 (2011)

Based on this expertise, the UGent research group "Organic and Biomimetic Chemistry Research" of Prof. Madder became one of the twelve European partners in the Marie Curie Training Network project MMBio ( Molecular Tools for Nucleic Acid Manipulation for Biological Intervention ) focusing on genetic drugs by designing systems to interfere therapeutically with gene expressing in living cells.


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