Peptide Formation in the Presence of a Metal Ion Protecting Group. 4. Synthesis of Penta- and Hexapeptide Sequences with the Pentaamminecobalt(III) Complex

Article abstract of DOI:10.1021/ja00378a021

Kinetically inert metal ion protecting groups provide radically different approaches to the protection of the terminals and side chains of amino acids and peptides.Pentaamminecobalt(III) is a useful C-terminal protecting group for sequential peptide synthesis.This is demonstrated by the synthesis of a number of amino acid complexes of the type where R=hydrophilic, hydrophobic, aliphatic, and aromatic amino acid side chains.The reaction of these complexes with Boc-amino acid active esters or Boc symmetric anhydrides results in the formation of .The Boc group is removed with 95percent trifluoroacetic acid to form , which is further used for sequential peptide synthesis.Alternatively, the <(NH3)5Co^III-> group is selectively removed by rapid reduction with NaBH4 or NaHS to form the N-protected peptide fragment, <(AA)1(AA)2Boc>, under extremely mild conditions.Tests for racemization of the amino acid directly bound to cobalt showed no detectable loss of chirality of <(AA)1>.The detailed synthesis, monitoring, purification, and analysis of cobalt pentaammine derivatives of Leu-enkephalin (TyrGlyGlyPheLeu), Met-enkephalin (TyrGlyGlyPheMet) and the hexapeptide sequence HisGlyHisGlyHisGly are described and so is a general procedure for peptide synthesis with the cobalt(III) protecting group.The individual fragments of these peptide sequences are characterized by HPLC.The attractive features of the <(NH3)5Co^III-> protecting group include its color, tripositive charge, ease of introduction, and removal.Such properties are invaluable in the purification of synthetic peptides.