Expanding the functionality of proteins with genetically encoded dibenzo[b,f][1,4,5]thiadiazepine: a photo-transducer for photo-click decoration

Abstract

Genetic incorporation of novel noncanonical amino acids (ncAAs) that is specialized for photo-click reaction empowers orthogonal and site-specific functionalization of proteins in living cells precisely under photo-control. However, development of...

Fluorescence turn-on by photoligation – bright opportunities for soft matter materials

“…107 The in situ photo-generation of the ring-strain structure thus enables visible light acceleration of bioorthogonal ligation in cellular environment. 108,109 However, the resultant 1,3-dipole adducts do not possess fluorescent properties, and thus a fluorogenic dye was required for labelling of the targeted biomacromolecules.…”

Dibenzo[b,f][1,4,5]chalcogenadiazepine Photoswitches: Conversion of Excitation Energy into Ring Strain

“…When utilized as a dipolarophile, the strained E ‐DBTD could also facilitate the rate of [3+2] cycloaddition with nitrilimine in the photo‐click reaction (up to 1.6±0.16×10 5 M −1 s −1 , 33.6‐fold faster than TCO) [27] . Unlike ring‐strain preloaded dipolarophiles (including TCO, [43] bicyclo[6.1.0]non‐4‐yne [47, 48] and dibenzocyclooctyne), [49] the in situ ring‐strain loading on E ‐DBTD via 405 nm laser enables dynamic and spatiotemporal control, thus minimizing undesired deactivation by nucleophiles in complex living context and improving precision of related bioorthogonal ligation [50] . Interestingly, the tricyclic core of DBTD was proven to be a novel skeleton for design of antioxidant inducer for neuroprotection with sub‐micromole activity, [28] and muscarinic receptor antagonist as antidepressant [51] .…”

“…[27] Unlike ring-strain preloaded dipolarophiles (including TCO, [43] bicyclo[6.1.0]non-4-yne [47,48] and dibenzocyclooctyne), [49] the in situ ring-strain loading on E-DBTD via 405 nm laser enables dynamic and spatiotemporal control, thus minimizing undesired deactivation by nucleophiles in complex living context and improving precision of related bioorthogonal ligation. [50] Interestingly, the tricyclic core of DBTD was proven to be a novel skeleton for design of antioxidant inducer for neuroprotection with sub-micromole activity, [28] and muscarinic receptor antagonist as antidepressant. [51] Despite these appealing features, it is still challenging to see what structural modification can significantly affect the photo-switching nature, and to what extent the energy harvesting efficiency can be achieved.…”

Photo-regulated genetic encoding of dibenzo[c,g][1,2]diazocine on proteins via configuration switching

“…12 The morphology of cis -DBDAA resembles an encodable cis -DBTDA 18 in a bowl-shape (Fig. S4, ESI†), which enables us to reconstruct and evolve the pyrrolysyl-tRNA synthetase/tRNA CUA pair from the available Mm DBTDARS mutation library 18 for decent fidelity. Therefore, six key residues (Fig.…”

“…20 The W417T mutation was retained for potential lone pair–π interactions between the –OH and the distal phenyl of c DBDAA. 18 Accordingly, site-directed mutagenesis was performed on residues, A302T, Y384F and W417T. The 401 site was defined as either Val or Leu in combination with a small-intelligent mutation library randomized on both N346 and C348 sites, avoiding biased probability of the codon redundancy in E. coli .…”