The chemistry of diazocompounds has generated a huge breadth of applications in the field of organic synthesis. Their versatility combined with their tuneable reactivity, stability and chemoselectivity makes diazo compounds desirable reagents for chemical biologists. Here, we describe a method for the precise installation of diazo-handles on proteins and antibodies in a mild and specific approach. Subsequent 1,3- cycloaddition reactions with strained alkynes enable both bioimaging through an in-cell ‘click’ reaction and probing of the cysteine proteome in cell lysates. The selectivity and efficiency of these processes makes these suitable reagents for chemical biology studies
