Community Research and Development Information Service - CORDIS

FP7

IODONIUM-CLICK Result In Brief

Project ID: 628381
Funded under: FP7-PEOPLE
Country: United Kingdom

Iodonium salts for bioconjugation

Diaryliodonium salts are hypervalent organoiodine compounds that are non-toxic, stable and have excellent selectivity in reactions. EU funded researchers made potentially paradigm-shifting advances in the field of bioconjugation chemistry using these salts.
Iodonium salts for bioconjugation
During the course of the IODONIUM-CLICK (Development of Iodonium salts into a versatile class of bioconjugation reagents) project, researchers discovered an iodonium salt with exceptional reactivity characteristics and good stability. Furthermore, it interacted with nucleophiles in mild conditions enabling an astonishing array of manipulability in functionality. They worked on adapting this functionality for conjugation to the amino acid methionine via click chemistry.

Preliminary results demonstrated that the concept of functionalising a methionine-containing dipeptide is viable even in water. Researchers further optimised this biorthogonal reaction with a yield exceeding 95 %.

IODONIUM-CLICK members then comprehensively investigated the substrate scope of the methionine conjugation reaction. Studies revealed at least four large medicinal polypeptides and four proteins with high conversion levels to the sulfonium conjugate form.

Studies on the diazo transfer reaction revealed several biologically relevant functional groups that can be transferred to proteins for applications in labelling. Importantly, these protein-sulfonium conjugates also demonstrate complementarity with contemporary functionalisation strategies.

A preliminary finding with immense potential, studies on the use of metal catalysis revealed the possibility for controllably reversing methionine-ligation. For instance, the Staudinger-type ligation with the diazo moiety enabled a shift of the entire conjugate from methionine to the N-terminus. More specifically, native-chemical ligation and selective functionalisation of nitrogen in a protein will now be possible.

Project activities have demonstrated the possibility of functionalising an amino acid residue – something that was previously not thought achievable via bioconjugation chemistry. This has innumerable applications in biomedicine that include drug discovery and targeted drug delivery for diseases like cancer and Alzheimer's.

Related information

Subjects

Life Sciences

Keywords

Bioconjugation, Diaryliodonium salts, nuclophile, methionine, bioorthogonal
Record Number: 190618 / Last updated on: 2016-11-29