Synthetic peptide methods share in common the protection of amino acid terminals and side chains to help direct peptide formation. During peptide synthesis the properties of these protecting groups become vital to the success of the synthesis. Some of these protecting groups render peptide fragments insoluble and therefore limit the synthesis. Metal ion protecting groups are proposed to replace and complement other organic groups. Attractive features of metal ions include their charge, color, and ease of introduction and removal. The positive charge of the metal ion protecting group can be a handle which will significantly aid in the purification of the synthesized peptide at any stage during the synthesis. Kinetically inert metal ions can be as stable as organic protecting groups, yet can be easily removed under very mild conditions (by making use of their redox properties). We are proposing to use kinetically inert metal ions, especially ((NH3)5Co(III)-) and other cobalt (III) derivatives, to aid peptide synthesis in a variety of ways: (a) as a protecting group for C-and N-terminals; (b) as a protecting group for various amino acid side chains; (c) the incorporation of cobalt(III) onto a polymeric support is suggested to allow the removal of a peptide from the polymeric support under very mild conditions; and finally, (d) the subject of peptide synthesis in aqueous solution is approached using these water soluble metal ion protecting groups which can be removed under very mild conditions. Angiotensin II, an eight residue polypeptide, will be synthesized using cobalt(III) protecting groups to demonstrate the usefulness of this approach.
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