Recent Advances in Chemical Biology Using Benzophenones and Diazirines as Radical Precursors

Abstract

The use of light-activated chemical probes to study biological interactions was first discovered in the 1960s, and has since found many applications in studying diseases and gaining deeper insight into various cellular mechanisms involving protein–protein, protein–nucleic acid, protein–ligand (drug, probe), and protein–co-factor interactions, among others. This technique, often referred to as photoaffinity labelling, uses radical precursors that react almost instantaneously to yield spatial and temporal information about the nature of the interaction and the interacting partner(s). This review focuses on the recent advances in chemical biology in the use of benzophenones and diazirines, two of the most commonly known light-activatable radical precursors, with a focus on the last three years, and is intended to provide a solid understanding of their chemical and biological principles and their applications.

Photochemical modifications for DNA/RNA oligonucleotides

“…86 Benzophenones and acetophenones also can form UV-induced (C-C) cross-links with protein amino acids. 84 For example, terminal deoxynucleotidyl transferase enzyme could be crosslinked to 3 0 -tails of DNA containing benzophenones and acetophenones on N 4 -dC's using 365 nm light (Fig. 8) 87 Reaction characteristics.…”

“…UV irradiation (365 nm) of benzophenones generates C-O biradical through n-p* transition, which can lead either to photocrosslinking or its reversal, photocleavage. 84,85 The photocleavage reaction was rendered complete aer 10 min of irradiation at 365 nm. 86 Thermodynamic or structural characteristics.…”

New Trends in Diaziridine Formation and Transformation (a Review)

“…Non-substituted diaziridine (diaziridine without any substituent on the nitrogen atom, 1) was developed as a reagent for a variety of oxidative transformations [6] and employed in the synthesis of carbene-mediated photoaffinity-labeled photophores of 3H-diazirines [7][8][9][10]. The trend of using diaziridine 1 as a precursor for the diazirine photoaffinity probe has been progressively updated until the present day, and a series of reviews have discussed it since the 2010s [7,[11][12][13][14][15]. Although the chemistry of N-monosubstituted diaziridine 2 has not been studied as extensively as that of non-substituted diaziridine 1, there are examples documenting its application as an N-transfer reagent with α,β-unsaturated amides to form stereopure aziridines [16].…”

Identification of photocrosslinking peptide ligands by mRNA display

“…10 A variety of chemistries can be used for the photoactivatable moiety, including benzophenones (Bpa), diazirines and aryl azides. 4,[11][12][13] Bpa is frequently used, due to its stability, 2 relatively mild activation conditions (365 nm light), and low reactivity with water. 14,15 In addition to its use in probes, an amino acid containing Bpa, p-benzoyl-L-phenylalanine (pBpa), has been successfully incorporated into proteins through genetic code reprogramming to study protein-protein interactions in vitro and in vivo.…”

“…Current methods often rely on rational design using existing ligands and information on their target binding mode. 5,12,18,19 This approach frequently results in low photocrosslinking efficiency, even when basing the probe on a high affinity ligand. A more efficient discovery approach would involve a method to directly screen large numbers of compounds for their ability to photocrosslink to a target of interest.…”