Ultra-inert lanthanide chelates as mass tags for multiplexed bioanalysis

• DOI: 10.1038/s41467-024-53867-1
• Publication Date: 2024-11-13T23:21:31Z
• Authors: Tomáš David; Miroslava Šedinová; Aneta Myšková; Jaroslav Kuneš; Lenka Maletínská; Radek Pohl; Martin Dračínský; Helena Mertlíková...; Karel Čížek; Blanka Klepetářová; Miroslava Litecká; Antonín Kaňa; David Sýkora; Adam Jaroš; Michal Straka; Miloslav Polasek
• Keywords: Bioanalysis; DOTA; Biomolecule; Inert

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