Synthesis of 2‐14C‐iminothiolane and 2‐13C,15N‐iminothiolane (Traut's reagent) |
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| Authors: | Michael Wallace Alban J. Allentoff John Brailsford Sharon Gong Samuel Bonacorsi Jr. Frank Rinaldi |
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| Affiliation: | 1. Discovery Chemistry Platforms‐Radiochemistry, Bristol‐Myers Squibb, Princeton, NJ, USA;2. Pharmaceutical Research and Development, Bristol‐Myers Squibb, New Brunswick, NJ, USA |
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| Abstract: | 2‐Iminothiolane has found utility in the growing area of antibody–drug conjugates by serving as a lysine‐thiolating agent and the junction between the antibody and the cytotoxic payload during random conjugation of a monoclonal antibody. 2‐14C‐Iminothiolane was prepared from commercially available [14C]KCN using a four‐step sequence in an overall 10% radiochemical yield. Stable‐labeled 2‐13C,15N‐iminothiolane was also prepared from [13C15N]KCN in a similar manner. The. labeled Traut's reagent produced by this sequence showed comparable reactivity as the commercially available unlabeled reagent with a representative monoclonal antibody and could serve as highly informative analytical tools to investigate antibody–drug conjugate formation via the random conjugation process. |
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| Keywords: | methyl 4‐mercaptobutyrimidate Traut's reagent 2‐iminothiolane monoclonal antibodies |
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