Synthesis of Peptides Containing Unnatural, Metal-Ligating Residues: Aminodiacetic Acid as a Peptide Side Chain

Article abstract of DOI:10.1021/jo00014a006

Peptides possessing a pair of residues separated by one turn in the α-helical conformation and potentially capable of ligating a single metal ion in aqueous solution were designed.It was predicted that the resulting cross-link would shift toward α-helix the random coil/α-helix equilibrium.The syntheses of 10 peptides Ac-Ada^lAla_mAda^l(Ala₄GluLys)_n-NH2 where Ada^l is an L-α-amino acid residue with an aminodiacetic acid bearing side chain, -(CH2)_lN(CH2CO2H)2 (with values of l, m and n as follows: 1, 2, 3 (1); 1, 3, 1 (2a); 1, 3, 2 (2b); 1, 3, 3 (2c); 2, 2, 3 (3); 2, 3, 3 (4); 3, 2 ,3 (5); 3, 3, 3 (6); 4, 2, 3 (7); 4, 3, 3 (8) are described using Boc chemistry on p-methylbenzhydrylamine resin.The aminodiacetic acid bearing residues were incorporated with side chains protected as the dibenzyl esters.To avoid side reactions, residues Ada^l for l=1 and 2 were incorporated by a block approach.Peptide structures were confirmed by observation of the predicted parent ions in the FAB MS.The circular dichroism spectra of several of these peptides that possess a pair of metal-ligating residues separated by two or three intervening residues have previously been shown to undergo changes on addition of metal ions consistent with appreciable enhancement of helix content.