Methods for Enhancing Ring Closing Metathesis Yield in Peptides: Synthesis of a Dicarba Human Growth Hormone Fragment

  • Bianca J. van Lierop
  • Amanda N. Whelan
  • Sofianos Andrikopoulos
  • Roger J. Mulder
  • W. Roy Jackson
  • Andrea J. Robinson
Article

DOI: 10.1007/s10989-010-9215-y

Cite this article as:
van Lierop, B.J., Whelan, A.N., Andrikopoulos, S. et al. Int J Pept Res Ther (2010) 16: 133. doi:10.1007/s10989-010-9215-y

Abstract

Ruthenium-alkylidene catalysed ring closing metathesis (RCM) provides a convenient method for the synthesis of cyclic dicarba peptide analogues. Sequences devoid of turn-inducing residues, however, can often fail to cyclise. A combination of pseudoproline (ΨPro) insertion and microwave irradiation can be used to enhance RCM yield in these problematic sequences. This strategy is illustrated in the synthesis of a dicarba human growth hormone (hGH) fragment. The structural changes associated with cystine to dicarba replacement were found to change the metabolic profile of the peptide.

Keywords

Anti-obesity AOD9604 Cyclic peptides Dicarba peptides Ring closing metathesis (RCM) Microwave irradiation Pseudoproline (ΨPro) residues 

Supplementary material

10989_2010_9215_MOESM1_ESM.pdf (36 kb)
Supplementary material 1 (PDF 35 kb)

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Bianca J. van Lierop
    • 1
  • Amanda N. Whelan
    • 1
    • 2
  • Sofianos Andrikopoulos
    • 3
  • Roger J. Mulder
    • 2
  • W. Roy Jackson
    • 1
    • 4
  • Andrea J. Robinson
    • 1
  1. 1.School of ChemistryMonash UniversityClaytonAustralia
  2. 2.CSIRO Molecular and Health TechnologiesClayton SouthAustralia
  3. 3.Department of Medicine, Austin Health/Northern HealthHeidelberg Repatriation Hospital, The University of MelbourneHeidelbergAustralia
  4. 4.Centre for Green ChemistryMonash UniversityClaytonVICAustralia

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