42563-41-7Relevant academic research and scientific papers
Tuning Isonitrile/Tetrazine Chemistry for Accelerated Deprotection and Formation of Stable Conjugates
Xu, Minghao,Deb, Titas,Tu, Julian,Franzini, Raphael M.
, p. 15520 - 15529 (2019)
The isocyano group is a valuable functionality for bioorthogonal reactions because it rapidly reacts with tetrazines to either form stable conjugates or release payloads from 3-isocyanopropyl groups. Here we provide mechanistic insights into the dissociative steps that follow the initial cycloaddition and analyze how structural modifications affect these processes. Three main outcomes of this study have important implications for designing such groups for bioorthogonal applications. First, anion-stabilizing substituents at C-2 of the 3-isocyanopropyl group promote β-elimination and accelerate deprotection. Second, tetrazines with bulky substituents form stable imine conjugates even with primary isonitriles that are otherwise rapidly hydrolyzed. Third, the elimination step is independent from hydrolysis to the aldehyde and instead can occur directly from the imine intermediate. These findings will allow tuning the structures of tetrazine and isonitrile reactants for application in bioorthogonal ligation and release chemistry.
RAPIDLY RELEASED BIOORTHOGONAL CAGING GROUPS
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Page/Page column 36-37, (2019/12/25)
Bioorthogonal molecules are disclosed and described. A bioorthogonal a molecule having a structure according to: Formula (I); where R2, R3, and R4 are independently selected from H, a substituted or unsubstituted C1/
