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Using cyclic peptide mixtures as probes for metal ion host-guest interactions

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Summary

Mixtures of cyclic peptides, formed by head-to-tail cyclizations of side-chain resin-bound linear sequences, have been prepared using solid-phase synthesis. Fast atom bombardment mass spectrometry of cyclic peptides with various metal ions can reveal preferred modes of host-guest patterns, albeit in a nonquantitative manner. This approach could prove useful for more rapid screening of potential peptide ionophores. A cyclic heptapeptide with a dipeptide tail proved to be a particularly effective host for a Ca2+ ion; in a small three-component mixture, cyclo[Gly-Asp-d-Pro-Xxx-Asp-d-Pro-Asp(Aca-Phe-NH2)], binding to Ca2+ varied from Xxx=N-MeAla>Gly≈Sar. In a 15-component mixture, cyclo[Pro-Xxx-Asn-Pro-Xxx-Asn] where Xxx=Ala, Glu, Leu, Lys or Phe, there were no significant differences with respect to binding to metal ions. We believe this to be the first reported use of cyclic peptide libraries for screening metal ions to discern host-guest relationships.

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Abbreviations

Aca:

aminocaproic acid

Boc:

tert-butyloxycarbonyl

BOP:

benzotriazolyloxy-tris(dimethylamino)phosphonium hexafluorophosphate

DCM:

dichloromethane

DIEA:

diisopropylethylamine

DMF:

N,N-dimethylformamide

ESI:

electrospray ionization

FABMS:

fast atom bombardment mass spectrometry

pMBHA:

4-methylbenzhydrylamine

TFA:

trifluoroacetic acid

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Authors and Affiliations

  1. Department of Chemistry, University of Louisville, 40292, Louisville, KY, U.S.A.

    Jian J. Chen & Arno F. Spatola

  2. High Resolution Mass Spectrometry Facility, University of Iowa, 52242, Iowa City, IA, U.S.A.

    Lynn M. Teesch

Authors
  1. Jian J. Chen
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  2. Lynn M. Teesch
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  3. Arno F. Spatola
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Additional information

This paper is based on a presentation given at the Symposium on Peptide Structure and Design as part of the 31st Annual ACS Western Regional Meeting held in San Diego, CA, USA, October 18–21, 1995.

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Chen, J.J., Teesch, L.M. & Spatola, A.F. Using cyclic peptide mixtures as probes for metal ion host-guest interactions. Lett Pept Sci 3, 17–24 (1996). https://doi.org/10.1007/BF00131081

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  • DOI: https://doi.org/10.1007/BF00131081

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