One common method involves diluting the reduced D-polypeptide chain from chaotropic agents in the presence of reduced and oxidized thiols as redox reagents, as reported in the synthesis of D-rC5a. [37] However, misfolded D-protein often arises as thermodynamically trapped by-products containing mismatched disulfide bonds and adducts with thiol reagents. Oxidation by air or DMSO has been used, following careful optimization of buffer additives, reagent concentrations, and pH. However, this method often results in low yields (typically <50%), requires large solvent volumes, and proceeds over several days. To gain additional control, orthogonal cysteine protection followed by pairwise cysteine oxidation may be used. Recently, an orthogonal cysteine protection scheme was developed, encoding a rapid system for disulfide oxidation (Table , Entry 23). Using palladium and UV light mediated deprotections, it was shown that up to three correctly paired disulfide bonds could be formed in less than 13 minutes. The use of trityl (Trt) and acetamidomethyl (Acm) protecting groups has been reported for formation two disulfide bonds in a D-protein (Table , Entry 23). Another protecting group that can be used is the 2-nitrobenzyl group but must be chemically synthesized (Table , Entry 23). Disulfide bond formation can also be directed without the use of chaotropic agents or orthogonal protection schemes, such as cysteinepenicillamine pairings or repeat-proline (CPPC) motifs. Figure : Examples of disulfide-rich D-proteins prepared by chemical synthesis, with structures resolved by racemic protein crystalloraphy.