Metallopeptide design: Tuning the metal cation affinities with unnatural amino acids and peptide secondary structure
Journal
Journal of the American Chemical Society
Journal Volume
118
Journal Issue
46
Pages
11349-11356
Date Issued
1996
Author(s)
Abstract
The ability to tune the metal binding affinity of small peptides through the incorporation of unnatural multidentate α-amino acids and the preorganization of peptide structure is illustrated. Herein, we describe the exploitation of a family of α-amino acids that incorporate powerful bidentate ligands (bipyridyl and phenanthrolyl groups) as integral constituents of the residues' side chains. The residues involved are the 6-, 5-, and 4-substituted (S)-2-amino-3-(2,2'-bipyridyl)propanoic acids (1, 6Bpa;2, 5Bpa; 3, 4Bpa), (S)-2-amino-3-(1,10-phenanthrol-2-yl)propanoic acid (4, Fen), and a novel neocuproine-containing α-amino acid, (S)-2-amino-3-(9-methyl-1,10-phenanthrol-2-yl)propanoic acid (5, Neo). Within this family of amino acids, variations in metal binding due to the nature of the ring system (2,2'-bipyridyl or 1,10-phenanthrolyl) and the point of attachment to the amino acid β-carbon are observed. Additionally, the underlying peptide architecture significantly influences binding for peptides that include multiple metal-ligating residues. These differences in affinity arise from the interplay of ligand type and structural preorganization afforded by the peptide sequence, resulting in dissociation constants ranging from 10-3 to < 10-6 M for Zn(II). These studies illustrate that significant control of metal cation binding affinity, preference, and stoichiometry may be achieved through the use of a wide variety of native and unnatural metal-coordinating amino acids incorporated into a polypeptide architecture.
SDGs
Type
journal article