Ultra-inert lanthanide chelates as mass tags for multiplexed bioanalysis (Nov 2024).

Journal: Nature Communications

Article link: https://doi.org/10.1038/s41467-024-53867-1

Authors: Tomáš David 1 , Miroslava Šedinová 1 , Aneta Myšková 1,2, Jaroslav Kuneš 1,3, Lenka Maletínská 1 , Radek Pohl 1 , Martin Dračínský 1 , Helena Mertlíková-Kaiserová1 , Karel Čížek1 , Blanka Klepetářová1 , Miroslava Litecká 4 , Antonín Kaňa 2 , David Sýkora 2 , Adam Jaroš 1 , Michal Straka1 & Miloslav Polasek 1

1 Institute of Organic Chemistry and Biochemistry, Czech Academy of Sciences, Prague, Czech Republic. 2 University of Chemistry and Technology Prague, Prague, Czech Republic. 3 Institute of Physiology, Czech Academy of Sciences, Prague, Czech Republic. 4 Institute of Inorganic Chemistry, Czech Academy of Sciences, Husinec-Řež, Czech Republic

Abstract: “Coordination compounds of lanthanides are indispensable in biomedical applications as MRI contrast agents and radiotherapeutics. However, since the introduction of the chelator DOTA four decades ago, there has been only limited progress on improving their thermodynamic stability and kinetic inertness, which are essential for safe in vivo use. Here, we present ClickZip, an innovative synthetic strategy employing a coordination-templated formation of a 1,5-triazole bridge that improves kinetic inertness up to a million-fold relative to DOTA, expanding utility of lanthanide chelates beyond traditional uses. Acting as unique mass tags, the ClickZip chelates can be released from (biological) samples by acidic hydrolysis, chromatographically distinguished from interfering lanthanide species, and sensitively detected by mass spectrometry. Lanthanides enclosed in ClickZip chelates are chemically almost indistinguishable, providing a more versatile alternative to chemically identical isotopic labels for multiplexed analysis. The bioanalytical potential is demonstrated on tagged cell-penetrating peptides in vitro, and anti-obesity prolactin-releasing peptides in vivo.”