Facile preparation of disulfide-bridged peptides using the polymer-supported oxidant CLEAR-OX.
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 identical with Ellman's reagent), when attached to polyethylene glycol-polystyrene (PEG-PS), 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 Cross-Linked Ethoxylate Acrylate Resin (CLEAR) supports, because of their compatibility with both organic and aqueous solvent mixtures. The resultant new tool, termed CLEAR-OX, 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.
Darlak
K
K
Peptides International, Inc., Louisville, KY 40299, USA. kdarlak@pepnet.com
Wiegandt Long
D
D
Czerwinski
A
A
Darlak
M
M
Valenzuela
F
F
Spatola
A F
AF
Barany
G
G
D000180:Acrylic Resins / Q000737:chemistry; D003432:Cross-Linking Reagents / Q000737:chemistry; D004220:Disulfides / Q000737:chemistry*; D004228:Dithionitrobenzoic Acid / Q000737:chemistry; D015394:Molecular Structure; D016877:Oxidants / Q000737:chemistry*; D010084:Oxidation-Reduction; D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D014579:Urotensins / Q000819:agonists / Q000037:antagonists & inhibitors
D000180:Acrylic Resins; D003432:Cross-Linking Reagents; D004220:Disulfides; D016877:Oxidants; D010455:Peptides; D014579:Urotensins; C029677:urotensin II; D004228:Dithionitrobenzoic Acid