Biomimetic chemistry on tandem protein/lipid damages under reductive radical stress

The study of radical stress in the biological environment needs a comprehensive vision of all possible reactive species and their mechanisms. Among them, reductive stress is evaluated for its selective target of sulfur-containing compounds. The selective attack of reducing species like H-center dot atoms or e(aq)(-)/H+ to sulfur-containing amino acid residues has been proved in different substrates, peptides and proteins. The transformations include methionine to a-aminobutyric acid and cysteine/cystine residues to alanine, as recognized in several sequences so far, such as RNase A, lysozyme, Met-enkephalin, amyloid beta-peptide and metallothioneins. The amino acid desulfurization is accompanied by the formation of low-molecular-weight sulfur-centered radicals that may cause geometrical cis-trans isomerization of unsaturated fatty acid residues in lipid bilayer. Thus, tandem protein/lipid damage is accomplished. Progress in research has given us a more comprehensive overview of the protein modifications and their roles, and the chemical biology approach will make its vital contribution to the study of free radical reactions, linking chemistry to biology and medicine.