TMTHSI, a superior 7-membered ring alkyne containing reagent for strain-promoted azide-alkyne cycloaddition reactions

Jimmy Weterings; Cristianne J F Rijcken; Harald Veldhuis; Tommi Meulemans; Darya Hadavi; Matt Timmers; Maarten Honing; Hans Ippel; Rob M J Liskamp

doi:10.1039/d0sc03477k

TMTHSI, a superior 7-membered ring alkyne containing reagent for strain-promoted azide-alkyne cycloaddition reactions

Chem Sci. 2020 Aug 10;11(33):9011-9016. doi: 10.1039/d0sc03477k.

Authors

Affiliations

¹ Cristal Therapeutics Oxfordlaan 55 6229 EV Maastricht The Netherlands robert.liskamp@cristaltherapeutics.com.
² Mercachem Kerkenbosch 1013 6546 BB Nijmegen The Netherlands.
³ The Maastricht Multimodal Molecular Imaging Institute (M4I), Maastricht University Universiteitssingel 50 6229 ER Maastricht The Netherlands.
⁴ Department of Biochemistry, CARIM, Maastricht University Universiteitssingel 50 6229 ER Maastricht The Netherlands.
⁵ School of Chemistry, Joseph Black Building, University of Glasgow University Avenue Glasgow G12 8QQ UK robert.liskamp@glasgow.ac.uk.
⁶ Chemical Biology and Drug Discovery, Department of Pharmaceutics, Utrecht University Universiteitsweg 99 3584 CG Utrecht The Netherlands.

Abstract

We describe the development of TMTH-SulfoxImine (TMTHSI) as a superior click reagent. This reagent combines a great reactivity, with small size and low hydrophobicity and compares outstandingly with existing click reagents. TMTHSI can be conveniently functionalized with a variety of linkers allowing attachment of a diversity of small molecules and (peptide, nucleic acid) biologics.