Maintaining Biological Activity by Using Triazoles as Disulfide Bond Mimetics

摘要

Disulfide bonds constitute an abundant and important structural element in the folding of proteins and peptides. By forming macrocycles, the three-dimensional structure of proteins and peptides can be stabilized and rigidified. For peptides in particular, the biological activity of these compounds is closely associated with the correct folding of the structure. Despite its stabilizing effect in peptides and proteins, the disulfide bridge itself is rather unstable. Disulfide isomerases, as well as reducing agents and thiols, can affect this covalent bond and can lead to structural rearrangement with a complete loss of activity. The replacement of this essential structural element by bioisosteric, and hydrolytically and reductively stable substitutes is therefore of great interest.