The goal of this review has been to present different chemical approaches for the formation of disulfide bonds in synthetic peptides and small proteins. Three general types of approaches have been described: (1) oxidation starting from the unprotected thiols; (2) oxidation starting from protected thiols; and (3) directed methods for formation of unsymmetrical disulfides. Individual or sequential disulfide-forming reactions can be carried out in solution or on a polymeric support. Overall yields and purities of products depends on protecting group combinations chosen, precise reaction conditions, and the targeted structure. Although no procedure can be guaranteed to give outstanding results for all cases, there are sufficient options available to support an optimistic view that one or more approaches can be optimized.
Bibliographical noteFunding Information:
We thank co-workers and colleagues, in particular Dr. Lin Chen, for sharing experiences regarding peptide disulfide chemistry. Preparation of this review and underlying experimental work were supported by the National Institutes of Health (GM 43552). I. A. gratefully acknowledges support via a National Science Foundation Graduate Fellowship.
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