Facile preparation of disulfide-bridged peptides using the polymer-supported oxidant CLEAR-OXTM

Authors

  • K. Darlak,

    1. K. Darlak, D. W. Long, A. Czerwinski, M. Darlak, and F. Valenzuela, Peptides International, Inc., Louisville, KY 40299, USA.
      G. Barany, Department of Chemistry, University of Minnesota, Minneapolis, MN 55455, USA.
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  • D. Wiegandt Long,

    1. K. Darlak, D. W. Long, A. Czerwinski, M. Darlak, and F. Valenzuela, Peptides International, Inc., Louisville, KY 40299, USA.
      G. Barany, Department of Chemistry, University of Minnesota, Minneapolis, MN 55455, USA.
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  • A. Czerwinski,

    1. K. Darlak, D. W. Long, A. Czerwinski, M. Darlak, and F. Valenzuela, Peptides International, Inc., Louisville, KY 40299, USA.
      G. Barany, Department of Chemistry, University of Minnesota, Minneapolis, MN 55455, USA.
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  • M. Darlak,

    1. K. Darlak, D. W. Long, A. Czerwinski, M. Darlak, and F. Valenzuela, Peptides International, Inc., Louisville, KY 40299, USA.
      G. Barany, Department of Chemistry, University of Minnesota, Minneapolis, MN 55455, USA.
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  • F. Valenzuela,

    1. K. Darlak, D. W. Long, A. Czerwinski, M. Darlak, and F. Valenzuela, Peptides International, Inc., Louisville, KY 40299, USA.
      G. Barany, Department of Chemistry, University of Minnesota, Minneapolis, MN 55455, USA.
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  • A. F. Spatola,

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    • The remaining authors dedicate this paper to the memory of Arno F. Spatola (May 9, 1944–July 5, 2003). Arno was a persuasive champion of CLEAR as a commercially viable material for important applications in peptide science.

  • G. Barany

    1. K. Darlak, D. W. Long, A. Czerwinski, M. Darlak, and F. Valenzuela, Peptides International, Inc., Louisville, KY 40299, USA.
      G. Barany, Department of Chemistry, University of Minnesota, Minneapolis, MN 55455, USA.
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  • Part of this work was reported in preliminary form at the 18th American Peptide Symposium, July 18–23, 2003, Boston, MA, USA (ref 1), and at the 8th International Symposium on Solid-phase Synthesis and Combinatorial Libraries, September 2–6, 2003, London, England, UK (ref 2).

K. Darlak
Peptides International, Inc.
11621 Electron Drive
Louisville
KY 40299
USA
Tel.: 502-266-8787
Fax: 502-267-1329
E-mail: kdarlak@pepnet.com

Abstract

Abstract:  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-PSTM), 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-OXTM, 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.

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