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40790-AC3
Metal-Peptide Nanoassemblies
This project explores using the directional bonding properties of coordination compounds to orient self-assembling peptide structures. In earlier work by our group, a covalently crosslinked two-stranded alpha-helical coiled-coil was prepared, called Pal14C19ox, that had metal-binding 4-pyridylalanine residues located on opposite sides of its structure. It was found that reaction of this peptide with fac-Re(CO)3Br3 having two labile coordination sites adjacent to one another, produces a continuous series of metal-peptide products in which Re complexes were seen to bridge from 2 to > 5 coiled-coil units in linear chains. Later work showed how modification of the peptide sequence which placed two additional metal binding sites onto the surface of the coiled-coil produced metal-bridged four-helix bundle. Most recently, two amphipathic polypeptides were coordinated to the cis positions of a square planar Pt(II) complex in order to provide the metal center with two non-covalent oligomerization domains. This resulted in the formation of new metal-peptide nanoassemblies which are shown to exist as nanometer-sized spheres and fibrils. Construction of these assemblies was based on the 30-residue polypeptide AQ-Pal14 which was designed for its ability to self-assemble into the common protein oligomerization motif of a non-covalent coiled-coil, and modified to contain a metal-binding 4-pyridylalanine residue at its surface. When AQ-Pal14 was reacted with Pt(en), a new metal-peptide complex was formed in which two AQ-Pal14 peptides were coordinated to a single metal center as determined by SDS-PAGE and ESI-MS. When the reaction mixture was analyzed under non-denaturing conditions by HPSEC, it was found that all species present eluted at the column void volume, indicating the formation of very large metal-peptide assemblies This was verified by multiangle light scattering (MALS) which showed that the metal-peptide assemblies have a weight-averaged molecular mass and z-average root mean square radius of Mw= (7 ± 4) x 106 g/mol and Rz = (18 ± 4) nm, respectively. The presence of such nanometer scale assemblies was confirmed by transmission electron microscopy and atomic force microscopy which showed the existence of both spherical and fibrillar nanostructures.
