Photoredox‐Mediated Hydrogen Isotope Exchange Reactions of Amino‐Acids, Peptides, and Peptide‐Derived Drugs. Issue 56 (16th September 2020)

• Record Type: Journal Article
• Authors: Legros, Fabien; Fernandez‐Rodriguez, Patricia; Mishra, Anurag; Weck, Remo; Bauer, Armin; Sandvoss, Martin; Ruf, Sven; Méndez, María; Mora‐Radó, Helena; Rackelmann, Nils; Pöverlein, Christoph; Derdau, Volker
• Is Part Of: Chemistry. Volume 26:Issue 56(2020)
• Page Start: 12738
• Page End: 12742
• Publication Date: 2020-09-16
• Subjects: amino acids -- C−H activation -- hydrogen isotope exchange -- peptide drugs -- photocatalysis; Chemistry -- Periodicals; 540
• DOI: 10.1002/chem.202003464
• Languages: English
• ISSNs: 0947-6539

Abstract

Abstract: Hydrogen isotopically labelled compounds are essential diagnostic tools in drug research and development, as they provide vital information about the biological metabolism of drug candidates and their metabolites. Herein we report a photoredox‐initiated hydrogen atom transfer (HAT) protocol which efficiently and selectively introduces deuterium or tritium at C(sp 3 )−H bonds, utilizing heavy water (D2 O or T2 O) as the hydrogen isotope source, and a guanidine base. This protocol has been successfully applied to the incorporation of deuterium in several amino acids (lysine, glycine and proline) and small peptides. Finally, the method has been applied to tritium, because tritium‐labelled peptides are essential for application in biological experiments, such as ligand‐binding assays, or absorption, distribution, metabolism, and excretion (ADME) studies. Abstract : Oh, HIE there ! The reactivity and selectivity of light‐induced hydrogen isotope exchange (HIE) reactions of complex peptides is demonstrated. In one step to radioactive labeled peptides for bioimaging!