Reversible Control of Tetrazine Bioorthogonal Reactivity by Naphthotube mediated Host-Guest Recognition - for Chem
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ABSTRACT: Tetrazine-mediated inverse electron demand Diels-Alder (IEDDA) reactions are widely used ultrafast bioorthogonal reactions, and methods to control such reactions would be extremely useful. Here, we identified a high affinity host-guest pair between synthetic macrocyclic naphthotubes and phenyltetrazine and developed a molecular-recognition strategy for controlling tetrazine reactions by host-caging. Naphthotubes can recognize phenyltetrazine on various biomolecules with low-micromolar and sub-micromolar binding affinities, thus cage their IEDDA reactivity efficiently in a reversible manner. For tetrazine residues on proteins encoded by non-canonical amino acid mutagenesis, their positions could be computationally designed such that exposed residues could be reversibly caged, whereas semiburied residues that were resistant to caging retained their reactivity, thus allowing preparation of site-specific protein dual conjugates and dual protein labeling on living cells with IEDDA reactions. The reactivity of tetrazine can be further regulated in living animals. Our strategy is thus expected to expand the applications of tetrazine chemistry.
ORGANISM(S): Homo Sapiens
SUBMITTER: Tao Liu
PROVIDER: PXD042163 | iProX | Thu May 11 00:00:00 BST 2023
REPOSITORIES: iProX
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