Facile preparation of disulfide‐bridged peptides using the polymer‐supported oxidant CLEAR‐OX TM

• Published in: The journal of peptide research Vol. 63; no. 3; pp. 303 - 312
• Main Authors: Darlak, K., Wiegandt Long, D., Czerwinski, A., Darlak, M., Valenzuela, F., Spatola, A. F., Barany, G.
• Format: Journal Article
• Language: English
• Published: 01.03.2004
• ISSN: 1397-002X
• DOI: 10.1111/j.1399-3011.2004.00153.x

Formation of disulfide bonds in synthetic peptides is one of the more challenging transformations to achieve in peptide chemistry, in view of the possible formation of oligomeric by‐products and other side reactions, as well as occasional solubility problems in aqueous oxidizing media. It was shown previously that 5,5′‐dithiobis(2‐nitrobenzoic acid) (DTNB ≡ Ellman's reagent), when attached to polyethylene glycol‐polystyrene (PEG‐PS TM ), controlled‐pore glass (CPG), or modified Sephadex supports, was an effective oxidizing agent that promoted disulfide formation under mild conditions. More recently, this work was extended to C ross‐ L inked E thoxylate A crylate R esin (CLEAR) supports, because of their compatibility with both organic and aqueous solvent mixtures. The resultant new tool, termed CLEAR‐OX TM , was used to conveniently produce several model cyclic disulfides with improved purities and yields, when compared with solution oxidations. A particularly striking example was the gram‐scale oxidation of a urotensin II antagonist peptide containing a hindered penicillamine unit.