Disulfides in endogenous peptides and synthetic analogues of linear pe
ptides play an important role in the maintenance of conformational sta
bility. Chemical synthesis of the disulfide bond can be accomplished b
y several methods. Most of the methods require a low concentration of
substrates in the oxidation step to avoid dimerization and polymerizat
ion, and this can limit the scale of the synthesis. This article revis
es the most interesting methods and technical modifications of disulfi
de bond formation in the respect of their usefulness in scale up prepa
ration. Special attention is given to a ''reverse oxidation'' methodol
ogy what has been investigated recently by the authors.