Structurally optimized tetrazines for rapid biological labeling
Bioorthogonal chemical reactions are closely associated with the characteristics of “click” chemistry, occurring with high selectivity and fast reaction kinetics in vivo. Consequently, these reactions found use as multipurpose tools for chemical biology. The Inverse-electron-Demand Diels–Alder (iEDDA) reaction between tetrazines and strained alkenes is fairly new ligation reaction, which displays rates 3-7 orders of magnitude faster than many bioorthogonal reactions. High reaction rates, biocompatibility, together with the ability of tetrazines to quench fluorescence of some fluorophores, widely used for fluorescent labeling, and recover it after iEDDA reaction (Figure 1) make tetrazine derivatives unique and versatile tools for bioortogonal chemistry. Figure 2 is showcasing possible approach to modification of commonly used fluorophore as fluoresceine (A) with tetrazines and application of tetrazine derivatives in DNA encoded libraries technologies (DELT), as the core scaffolds (B).
Figure 1. General scheme of IeDDA ligation.
Figure 2. Tetrazine ligation of fluoresceine (A) and use of tetrazine core in DELT-compatible reaction (B).
Currently, we have synthesized 8 tetrazine-containing building blocks, that are available in our store on a gram scale.
We also have designed a library of tetrazine-containing building blocks. These molecules can be synthesized upon request.
- Cyclic sulfates and sulfamidates as alkylating reagents
- Saturated Bioisosteres for ortho-substituted Benzenes
- Aliphatic Trifluoroborates (-BF3) for C-C couplings
- Functionalized Vinyl Boronates for C-C couplings
- Unique 3D-shaped Spirocycles
- Water-soluble non-classical benzene mimics
- gem-Difluorinated Amines for Drug Design
- Fluorosulfates and Sulfamoyl Fluorides
- Alkyne-containing Linkers
- Structurally optimized tetrazines for rapid biological labeling
- Building blocks and linkers for PROTAC synthesis
- Heterocyclic Sulfonyl Fluorides
- Silicon-Containing Building Blocks
- Epoxides for Drug Design
- Analogues of CF3-Pyridine for Drug Design
- Piperazine Bioisosteres for Drug Design
- Sugar-like Building Blocks for Drug Design
- Cyclic Sulfonamides for Drug Design
- Morpholine Bioisosteres for Drug Design
- P(O)Me2-containing Building Blocks
- Saturated Bioisosteres of ortho-/meta-substituted Benzenes
- Saturated bioisosteres of para-substituted benzenes
- Sulfonyl fluorides (-SO2F)
- Oxetane-containing Building Blocks
- SF5-Building Blocks
- Stannanes for coupling reactions
- Sulfoximines for Drug Design
- Heterocyclic scaffolds
- Azide-linkers for Drug Design
- Unnatural Amino Acids
- Cubanes for Medicinal Chemistry
- Benzoxaboroles for Drug Design