Reversible control of tetrazine bioorthogonal reactivity by naphthotube-mediated host-guest recognition

Cao，Wenbing1,2; Wang，Haoyu1; Quan，Mao3,4; Li，Yuxuan1; Su，Yeyu1; Li，Yuhang1; Jiang，Wei4; Liu，Tao1

2023

10.1016/j.chempr.2023.05.034

Chem   Impact Factor & Quartile

2451-9308

2451-9294

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 and 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.

bioconjugation bioorthogonal reaction genetic code expansion host-guest recognition SDG3: Good health and well-being tetrazine

SCI

English

Others

National Key Research and Development Program of China[2021YFA0909900];National Key Research and Development Program of China[2022YFA0912400];National Natural Science Foundation of China[92156025];National Natural Science Foundation of China[92253301];Natural Science Foundation of Beijing Municipality[JQ20034];National Natural Science Foundation of China[U22A20332];

WOS:001094972500001

2-s2.0-85170043315

Scopus

1.State Key Laboratory of Natural and Biomimetic Drugs,Department of Molecular and Cellular Pharmacology,School of Pharmaceutical Sciences,Chemical Biology Center,Peking University,Beijing,38 Xueyuan Road, Haidian District,100191,China
2.College of Chemistry,State Key Laboratory of Elemento-Organic Chemistry,Nankai University,Tianjin,94 Weijin Road, Nankai District,300071,China
3.College of Materials Science and Engineering,Shenzhen University,Shenzhen,Xueyuan Blvd 1066,518060,China
4.Shenzhen Grubbs Institute,Department of Chemistry,and Guangdong Provincial Key Laboratory of Catalysis,Southern University of Science and Technology,Shenzhen,Xueyuan Blvd 1088,518055,China

Cao，Wenbing,Wang，Haoyu,Quan，Mao,et al. Reversible control of tetrazine bioorthogonal reactivity by naphthotube-mediated host-guest recognition[J]. Chem,2023,9(10):2881-2901.

Cao，Wenbing.,Wang，Haoyu.,Quan，Mao.,Li，Yuxuan.,Su，Yeyu.,...&Liu，Tao.(2023).Reversible control of tetrazine bioorthogonal reactivity by naphthotube-mediated host-guest recognition.Chem,9(10),2881-2901.

Cao，Wenbing,et al."Reversible control of tetrazine bioorthogonal reactivity by naphthotube-mediated host-guest recognition".Chem 9.10(2023):2881-2901.