Ultra-inert lanthanide chelates as mass tags for multiplexed bioanalysis

Area of Science:

• Inorganic Chemistry
• Bioanalytical Chemistry
• Radiochemistry

Background:

• Lanthanide coordination compounds are vital for MRI contrast agents and radiotherapeutics.
• Limited progress in chelator stability (e.g., DOTA) hinders safe in vivo application.
• Enhanced thermodynamic stability and kinetic inertness are crucial for in vivo lanthanide use.

Purpose of the Study:

• To introduce an innovative synthetic strategy, ClickZip, for lanthanide chelation.
• To significantly improve the kinetic inertness of lanthanide chelates beyond existing standards.
• To demonstrate the utility of ClickZip chelates in bioanalytical applications.

Main Methods:

• Developed ClickZip, a coordination-templated synthesis forming a 1,5-triazole bridge.
• Investigated kinetic inertness improvements compared to DOTA.
• Utilized acidic hydrolysis, chromatography, and mass spectrometry for detection and analysis.
• Applied ClickZip chelates to tag peptides for in vitro and in vivo studies.

Main Results:

• ClickZip enhances kinetic inertness up to a million-fold over DOTA.
• ClickZip chelates serve as unique mass tags, releasable by acidic hydrolysis.
• Lanthanide species are chromatographically separated from interfering ions and detected by mass spectrometry.
• Demonstrated bioanalytical potential using tagged cell-penetrating peptides and anti-obesity peptides.

Conclusions:

• ClickZip offers a significant advancement in lanthanide chelation technology.
• The enhanced kinetic inertness expands the utility of lanthanide chelates in biomedical fields.
• ClickZip chelates provide a versatile platform for sensitive, multiplexed bioanalysis.