Guillaume Clavé, "Application of the sulfo-click reaction in the field of nucleic acid chemistry"

When: 9. Oktober 2024, 16-17.30h

Where: LH3, Boltzmanngasse 1, 1090 Wien

Title: "Application of the sulfo-click reaction in the field of nucleic acid chemistry"
Guillaume Clavé, IBMM, Univ Montpellier, CNRS, ENSCM, Montpellier, France

Click reactions are fast, chemoselective and high-yielding covalent reactions between two reactive functions without generating hazardous byproducts.1 Such ideal reactions have found a wide range of applications2 in particular in the context of bioorthogonal chemistry.3 Despite the considerable growth in the number of available click reactions over the past two decades, there is ongoing development to overcome the limitations of existing reactions.4 The sulfo-click reaction is an emerging surrogate click reaction involving a thioacid that specifically reacts with a sulfonyl azide, resulting in the formation of an N-acylsulfonamide linkage. This reaction meets the criteria of click reactions, generates only sulfur and dinitrogen as byproducts, and is compatible with aqueous conditions. These characteristics are of particular interest in the field of nucleic acid chemistry. Additionally, the N- acylsulfonamide moiety arouses an increasing interest in the field of medicinal chemistry as an isostere of the carboxylic acid and phosphate functions.5

Guillaume Clavé and team recently developed the synthesis of original 4′-thioacid nucleoside analogues that opened the way to new interesting applications of the sulfo-click reaction.

Guillaume Clavé will present his endeavor taking advantage of the efficiency of the sulfo-click reaction for bioconjugation. Various sulfonyl azide derivatives were successfully conjugated to 4’- thioacid nucleosides under aqueous, biocompatible conditions. Subsequently, a series of molecules were synthesized with various potential therapeutic applications, exploiting the interesting properties of the N-acylsulfonamide linkage in medicinal chemistry.

1. H. C. Kolb, M. G. Finn and K. B. Sharpless, Angew. Chem. Int. Ed., 2001, 40, 2004-2021. 2. S. Chandrasekaran, Click reactions in organic synthesis, John Wiley & Sons, 2016.
3. E. M. Sletten and C. R. Bertozzi, Angew. Chem. Int. Ed., 2009, 48, 6974-6998.
4. N. K. Devaraj, ACS. Cent. Sci., 2018, 4, 952-959.
5. A. Ammazzalorso, B. De Filippis, L. Giampietro and R. Amoroso, Chem. Biol. Drug. Des., 2017, 90, 1094-1105.