Furan- and Triazolinedione-based Chemistries for Bio-orthogonal Protein Modification — ASN Events
  1. Schedule
  2. SESSION 2: Synthetic and Biosynthetic Technologies
  3. Furan- and Triazolinedione-based Chemistries for Bio-orthogonal Protein Modification

Furan- and Triazolinedione-based Chemistries for Bio-orthogonal Protein Modification (#6)

Laia Miret Casals 1 , Ewout De Geyter 1 , Jan H Meffert 1 , Annemieke Madder 1
  1. Department of Organic and Macromolecular Chemistry / Organic and Biomimetic Chemistry Research Group, Ghent University, Ghent, Belgium

Within OBCR, we have developed a highly selective and efficient furan-oxidation mediated crosslink technology which is applicable to peptide-protein, peptide-nucleic acid and nucleic acid interstrand crosslink scenarios.[1] Furan activation requires an oxidation trigger,[2] allowing spatiotemporal control of the crosslinking event.

We developed furan-modified peptide probes which can be used for efficient and selective crosslinking to natural protein targets.[3]  In the context of peptide ligand-receptor interactions, we have described, in live cells under normal growth conditions, selective crosslinking of furan-modified peptide ligands to their membrane receptor with zero toxicity, high efficiency and spatio-specificity.[5]

Different furan and triazolinedione based chemistries were further developed for versatile and site-selective modification of proteins and synthesis of bioconjugates.[6] The talk will highlight selected specific examples of these cross-linking and conjugation methodologies.

 

The work was supported by the FWO-Vlaanderen, the BOF-UGent and the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 721613 (MMBio) and No. 665501 (Pegasus2).

  1. 1 a) Carrette, L.L.G, Morii, T.; Madder, A. Bioconj. Chem. 2013, 24(12), 2008-2014; b) L. L. G. Carrette, E. Gyssels, N. De Laet and A. Madder. Chem Comm. 2016, 52, 1539.
  2. 2 a) Op de Beeck, M., and Madder, A. JACS 2012, 134, 10737–10740; b) De Laet, N., Llamas, E.M., and Madder, A. ChemPhotoChem 2018 2, 575–579;
  3. 3 a) Miret-Casals, L.; Vannecke, W.; Hoogewijs, Madder, A. et al. Chem. Comm., 2021, 57, 6054 – 6057; b) Miret Casals, L.; Van De Putte, S. ; Madder, A. et al. Frontiers in Chemistry, 2022. 9:799706.
  4. 4 a) Vannecke, Van Troys, Ampe & Madder, ACS Chemical Biology 2017, 2191; b) EP10196898.0.; c) EP 15176415.6.
  5. 5 a) Decoene, K. W.; Ünal, K.; Staes, A.; Zwaenepoel, O.; Gettemans, J.; Gevaert, K.; Winne, J. M.; Madder, A. Chemical Science, 2022, 13, 5390 – 5397. b) De Geyter, E.; Antonatou, E.; Kalaitzakis, D.; Madder, A. Chemical Science, 2021, 12, 5246 – 5252. EP 19160048.5.
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