Methods for Enhancing Ring Closing Metathesis Yield in Peptides: Synthesis of a Dicarba Human Growth Hormone Fragment
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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.
KeywordsAnti-obesity AOD9604 Cyclic peptides Dicarba peptides Ring closing metathesis (RCM) Microwave irradiation Pseudoproline (ΨPro) residues
The authors acknowledge the provision of an Australian Postgraduate Research Award (to B.J.v.L. and A.N.W.), AINSE Post Graduate Research Award (to B.J.v.L. and A.N.W.) and CSIRO Postgraduate Scholarship (to A.N.W.). We also thank the Australian Research Council and Circardian Technologies Ltd. for financial assistance.
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