Letters in Peptide Science

, Volume 7, Issue 1, pp 47–52

Application of solid-phase Ellman's reagent for preparation of disulfide-paired isomers of α-conotoxin SI

Article

DOI: 10.1007/BF02443562

Cite this article as:
Hargittai, B., Annis, I. & Barany, G. Lett Pept Sci (2000) 7: 47. doi:10.1007/BF02443562

Summary

Disulfide-paired regioisomers of α-conotoxin SI can be accessed by orthogonal schemes using the combination ofS-9H-xanthen-9-yl (S-Xan) andS-acetamidomethyl (S-Acm) groups for cysteine protection. Following solidphase assemblies of the linear precursors, the peptides were cleaved from the solid support concurrent with removal ofS-Xan protecting groups. The first disulfide bridges were formed in solution, using either the traditional DMSO method or a recently introduced approach featuring a solid-phase Ellman's reagent. The second disulfide bridges were oxidized by three different methods: reactions mediated by thallium trifluoroacetate, iodine, or a sulfoxide/silyl mixture. In general, yields depended primarily on which regioisomer was the target, rather than the specific chemistry used for either disulfide-forming step. However, the selectivities towards the desired regioisomers were reproducibly better using the solid-phase Ellman's reagent, by comparison to the DMSO method. In the most favorable cases, complete selectivity was achieved, while even in cases where the net results using DMSO gave considerable scrambling, the corresponding experiments with the solid-phase Ellman's reagent were more selective. Possible reasons why choice of oxidation method for the first step affects the selectivity at the second step are discussed.

Key words

α-conotoxin SI disulfide pairing orthogonal cysteine protection solid-phase Ellman's reagent 

Copyright information

© Kluwer Academic Publishers 2000

Authors and Affiliations

  1. 1.Department of ChemistryUniversity of MinnesotaMinneapolisU.S.A.

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