We have previously published a protocol for synthesizing orthogonally protected building blocks to be used as disulphide-bridge mimetics as well as schemes for the selective removal of any one of the four protecting groups on the building block. We have also shown that it is possible to introduce a carbon isostere of a disulphide bridge by utilizing ring-closing metathesis on allylglycine-residues included in the sequence of the peptide in place of cysteine residues, even though this significantly harder to achieve than anticipated. The RCM approach has the limitation of the product being a mixture of the E and Zisomers of the double bond, as proven by NMR analysis.In this work we present a method for using the building-block approach for including The disulphide bridge mimetics in a peptide. We also show that the replacement of the disulphide bridge with a non-natural building block does not significantly lower the biological activity compared to the parent peptide.

Introducing disulphide bridge mimicking building blocks into cyclic peptides

245th National Meeting (2013)

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