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Boron-Rich Biologics Enabled by Reactive Organic Carboranes.
Anže Jenko1, Urban Barbič1, Aljaž Renko1
1University of Ljubljana, Faculty of Chemistry and Chemical Technology, Department of Chemistry and Biochemistry, Večna pot 113, Ljubljana 1000, Slovenia.
JACS Au
|June 26, 2026
Summary
Researchers developed new organic carborane reagents for easy incorporation into molecules and proteins. These reagents create boron-rich antibody conjugates for potential use in boron neutron capture therapy (BNCT).
Area of Science:
- Boron chemistry
- Materials science
- Bioconjugation
Background:
- Carboranes possess unique structural and electronic properties, leading to diverse applications.
- Existing methods for incorporating carboranes into larger structures are limited, hindering their broader use.
Purpose of the Study:
- To develop versatile organic carborane reagents for efficient conjugation to biomolecules.
- To create novel carborane-peptide polymers and boron-rich antibody conjugates.
Main Methods:
- Synthesis of organic carborane reagents based on N-hydroxysuccinimide (NHS) esters.
- Conjugation of carborane reagents to amine-containing residues of small molecules and polypeptides.
- Functionalization of therapeutic antibodies with carborane reagents and analysis via mass spectrometry.
Main Results:
- Developed NHS ester-based carborane reagents for selective conjugation.
- Created carborane-peptide polymers and antibody conjugates with high boron content (up to 13 carboranes/antibody).
- Demonstrated that linker length is critical for loading efficiency and identified preferential lysine modification sites on antibodies.
Conclusions:
- The developed carborane reagents offer a versatile platform for creating hybrid materials and boron-rich antibody conjugates.
- These constructs retain antibody activity and show potential for antibody-drug conjugates and boron neutron capture therapy (BNCT).
- Lysine mapping provides a framework for optimizing antibody-drug conjugate design.
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