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Updated: Feb 13, 2026

Synthesis and Bioconjugation of Thiol-Reactive Reagents for the Creation of Site-Selectively Modified Immunoconjugates
Published on: March 6, 2019
Thiol-Reactive Bifunctional Chelators for the Creation of Site-Selectively Modified Radioimmunoconjugates with
Pierre Adumeau1,2, Maria Davydova1, Brian M Zeglis1,2,3,4
1Department of Chemistry , Hunter College of the City University of New York , New York , New York 10028 , United States.
Abstract:
Maleimide-bearing bifunctional chelators have been used extensively for the site-selective bioconjugation and radiolabeling of peptides and proteins. However, bioconjugates obtained using these constructs inevitably suffer from limited stability in vivo, a trait that translates into suboptimal activity concentrations in target tissues and higher uptake levels in healthy, nontarget tissues. To circumvent this issue, phenyloxadiazolyl methylsulfones have previously been reported as alternatives to maleimides for thiol-based ligations, but these constructs have scarcely been used in the field of radiochemistry. In this report, we describe the synthesis of two thiol-reactive bifunctional chelators for 89Zr and 177Lu based on a new, easy-to-make phenyloxadiazolyl methylsulfone reagent, PODS. Radioimmunoconjugates created using these novel bifunctional chelators displayed in vitro stability that was higher than that of their maleimide-derived cousins. More importantly, positron emission tomography imaging in murine models of cancer revealed that a 89Zr-labeled radioimmunoconjugate created using a PODS-bearing bifunctional chelator produced a rate of uptake in nontarget tissues that is significantly lower than that of its analogous maleimide-based counterpart.
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