Reaction of Azide Radicals with Amino Acids and Proteins

Summary

The azide radical N^·₃ reacts selectively with amino acids, in neutral solution preferentially with tryptophan (k(N^·₃ + TrpH) = 4·1 × 10⁹ dm³ mol⁻¹s⁻¹) and in alkaline solution also with cysteine and tyrosine (k(N^·₃ + CyS⁻) = 2·7 × 10⁹ dm³ mol⁻¹s⁻¹ and k(N^·₃ + TyrO⁻) = 3·6 × 10⁹ dm³ mol⁻¹s⁻¹). Oxidation of the enzyme yADH by N^·₃ involves primary attacks, mainly at tryptophan residues, and subsequent slow secondary reactions. N^·₃-induced inactivation of yADH is likely to occur upon oxidation of tryptophan residues in the substrate binding pocket (58-TrpH and 93-TrpH) since the substrate ethanol, although unreactive with N^·₃, protects yADH and since elADH, which does not contain tryptophan in the substrate pocket, is comparatively resistant against N^·₃-attack. N^·₃ exhibits low reactivity with nucleic acid derivatives and it is inert towards aliphatic compounds such as methanol and sodium dodecylsulphate.