Recent Applications of Diazirines in Chemical Proteomics

Abstract

The elucidation of substrate–protein interactions is an important component of the drug development process. Due to the complexity of native cellular environments, elucidating these fundamental biochemical interactions remains challenging. Photoaffinity labeling (PAL) is a versatile technique that can provide insight into ligand‐target interactions. By judicious modification of substrates with a photoreactive group, PAL creates a covalent crosslink between a substrate and its biological target following UV‐irradiation. Among the commonly employed photoreactive groups, diazirines have emerged as the gold standard. In this Minireview, recent developments in the field of diazirine‐based photoaffinity labeling will be discussed, with emphasis being placed on their applications in chemical proteomic studies.

The Application of Fluorine‐Containing Reagents in Structural Proteomics

“…developed the first fluorinated diazirines, the 3‐trifluoromethyl‐3‐phenyldiazirines (TPDs), for photolabeling. The effectiveness of diazirines in affinity‐labeling was recently reviewed . TPDs offer better chemical and thermal stability than other diazirines, (Figure a).…”

“…Brunner et al [4] developed the first fluorinated diazirines,t he 3-trifluoromethyl-3-phenyldiazirines (TPDs), for photolabeling.The effectiveness of diazirines in affinity-labeling was recently reviewed. [5] TPDs offer better chemical and thermal stability than other diazirines, ( Figure 1a). Theadjacent aryl and trifluoromethyl groups (-CF 3 ) stabilize the diazo intermediate formed on irradiation with UV light.…”

Fluorierte Reagenzien in der Strukturproteomik

“…Brunner und Mitarbeiter entwickelten die ersten fluorierten Diazirine – 3‐Trifluormethyl‐3‐phenyldiazirine (TPDs) – für die Photomarkierung . Die Effizienz von Diazirinen in der Affinitätsmarkierung wurde kürzlich von Lumb und Halloran untersucht . Gegenüber anderen Diazirinen bieten TPDs eine bessere chemische und thermische Stabilität (Abbildung a).…”

“…[3] [4] Die Effizienz von Diazirinen in der Affinitätsmarkierung wurde kürzlich von Lumb und Halloran untersucht. [5] Gegenüber anderen Diazirinen bieten TPDs eine bessere chemische und thermische Stabilität(Abbildung 1a). Die benachbarten Aryl-und Tr ifluormethyl (CF 3 )-Gruppen stabilisieren das Diazointermediat, das durch die UV-Bestrahlung gebildet wird.…”

A bifunctional amino acid to study protein–protein interactions

“…[4][5][6] Among all the frequently used photoreactive groups, diazirine is known for its small size and high reactivity. [7][8][9][10] These two features of diazirine ensure high crosslinking specicity and efficiency, as it can be installed close enough to the binding sites without inducing undesired steric hindrance, and thereby selectively and rapidly label the PPIs of interest upon photo-activation.…”