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Updated: Jan 26, 2026

Synthesis and Bioconjugation of Thiol-Reactive Reagents for the Creation of Site-Selectively Modified Immunoconjugates
Published on: March 6, 2019
Site-Selective Synthesis of Insulin Azides and Bioconjugates
Sobhana Babu Boga1, Shane W Krska1, Songnian Lin1
1Chemistry Capabilities for Accelerating Therapeutics , Merck & Co., Inc. , Kenilworth , New Jersey 07033 , United States.
Abstract:
A synthetic method to access novel azido-insulin analogs directly from recombinant human insulin (RHI) was developed via diazo-transfer chemistry using imidazole-1-sulfonyl azide. Systematic optimization of reaction conditions led to site-selective azidation of amino acids B1-phenylalanine and B29-lysine present in RHI. Subsequently, the azido-insulin analogs were used in azide-alkyne [3 + 2] cycloaddition reactions to synthesize a diverse array of triazole-based RHI bioconjugates that were found to be potent human insulin receptor binders. The utility of this method was further demonstrated by the concise and controlled synthesis of a heterotrisubstituted insulin conjugate.
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