Side Chain Fragmentation of N-Terminal Threonine or Serine Residue Induced through Intramolecular Proton Transfer to Hydroxy Sulfuranyl Radical Formed at Neighboring Methionine in Dipeptides

The reaction of hydroxyl radicals with Ser-Met and Thr-Met at slightly acidic to neutral pH results in the side chain fragmentation of the Ser and the Thr moiety into formaldehyde and acetaldehyde, respectively. The efficiency of this process depends on the concentration of the peptide and protons with maximum yields at low peptide concentrations at near neutral pH. Significantly less aldehyde formation is observed for the reaction of hydroxyl radicals with Ala-Met, Val-Met, Gly-Ser-Met, Met-Ser, Gly-Met-Ser, Ser-Leu, Gly-Thr-Met, and Gly-Met-Thr. These results indicate that the formation of aldehyde requires (i) an N-terminal Ser or Thr residue and (ii) the presence of Met in the sequence. The underlying mechanism involves an intramolecular proton transfer from the protonated N-terminal amino group to an initially formed hydroxy sulfuranyl radical at the Met residue. This process leads to the elimination of water and the simultaneous formation of a three-electron-bonded [>S[therefore]NH[sub 2]][sup +]-peptide intermediate which absorbs at [lambda][sub max] = 385 nm and has been identified by pulse radiolysis. This intermediate decays with t[sub 1/2] = 310 ns into aldehyde and an [alpha]-amino radical of the structure H[sub 2]N-C[sup [sm bullet]]H-C(= O)NH-peptide, which has been identified by ESR spectroscopy. 57 refs., 8 figs.