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 possiblereactive species and their mechanisms. Among them, reductive stress is evaluated for its selective target of sulfurcontainingcompounds. The selective attack of reducing species like Ho atoms or eaq-/H+ to sulfur-containing aminoacid residues has been proved in different substrates, peptides and proteins. The transformations include methionineto ?-aminobutyric acid and cysteine/cystine residues to alanine, as recognized in several sequences so far,such as RNase A, lysozyme, Met-enkephalin, amyloid ?-peptide and metallothioneins. The amino acid desulfurizationis accompanied by the formation of low-molecular-weight sulfur-centered radicals that may cause geometricalcis-trans isomerization of unsaturated fatty acid residues in lipid bilayer. Thus, tandem protein/lipid damage isaccomplished. Progress in research has given us a more comprehensive overview of the protein modifications andtheir roles, and the chemical biology approach will make its vital contribution to the study of free radical reactions,linking chemistry to biology and medicine.