Oxidative radicals (HO• or N3•) induce several di-tyrosine bridge isomers at the protein scale

Among protein oxidative damages, di-tyrosine bridges formation has been evidenced in many neuropathological diseases. Combining oxidative radical production by gamma radiolysis with very performant chromatographic separation coupled to mass spectrometry detection, we brought into light new insights of tyrosine dimerization. Hydroxyl and azide radical tyrosine oxidation leading to di-tyrosine bridges formation was studied for different biological compounds: a full-length protein (Delta 25-centrin 2), a five amino acid peptide (KTSLY) and free tyrosine. We highlighted that both radicals generate high proportion of dimers even for low doses. Surprisingly, no less than five different di-tyrosine isomers were evidenced for the protein and the peptide. For tyrosine alone, at least four distinct dimers were evidenced. These results raise some questions about their respective role in vivo and hence their relative toxicity. Also, as di-tyrosine is often used as a biomarker, a better knowledge of the type of dimer detected in vivo is now required.

Automated summary

This study investigated the formation of di-tyrosine bridges in different biological compounds through gamma radiolysis and chromatographic-mass spectrometry analysis, revealing the presence of multiple di-tyrosine isomers and raising questions about their respective roles and toxicity in vivo. A better understanding of the type of di-tyrosine detected in vivo is now necessary, especially considering its common use as a biomarker.