Evolving Trends in Transition Metal-Modified Receptor Design and Function - Designing Receptors for the Next Generation of Biosensors - page 238

Fig. 2 Proposed model for metal-directed assembly of a trimeric coiled coil [M(bpy-peptide) 3 ] 2+ .
A six-coordinate metal ion ( sphere ) tethers three 2,2 0 -bpy ligands covalently linked to amphiphilic
peptides ( left ), which drives hydrophobic collapse to yield the coiled coil structure ( right ).
Adapted with permission from [ 10 ]. Copyright 2004 American Chemical Society
HIV-1 [ 15 ]. The [M(bpy-peptide) 3 ] 2+ coiled coil structures were shown to display
receptor characteristics of the intact gp41 subunit by binding a small flanking
peptide from the gp41 C-heptad repeat. By labeling this C-peptide with a fluores-
cent probe, compounds that bind the metal-directed coiled coil and displace the
C-peptide were measured via FRET with a competitive inhibition assay. Impor-
tantly, this study suggests that [M(bpy-peptide) 3 ] 2+ motifs may serve as functional
surrogates for full-length fusion proteins of class 1 enveloped viruses that are
unsuitable for biophysical binding studies as the coiled coil regions of interest in
the native proteins are masked by outer domains.
The ability to direct tertiary structure stabilization of designed peptide sequences
through metal-ligand coordination provides biosensor researchers a powerful strat-
egy for constructing receptors with defined rigid three-dimensional topologies.
Further, it offers a facile route to synthetic receptors capable of discrete polyvalent
binding interactions that may display increased affinities over their monovalent
precursors. However, one potential limitation is the formation of multiple
stereoisomers based on the coordination geometry of the metal complex which
may complicate purification efforts. Regardless, it is anticipated that the molecular
surfaces of such ordered peptides will more closely mimic naturally occurring
protein recognition elements (i.e., ordered tertiary structures such as antigen-
binding clefts in antibodies) and lead to synthetic receptors with increased specific-
ity for a range of molecular targets.
Looking beyond oligopeptides, significant strides have also been made toward
metal-directed protein self-assembly with the overarching goal to be able to master
protein-protein interactions and access novel functional biomaterials [ 7 , 16 ]. Ulti-
mately, such designed protein interfaces coupled with designed metal-binding sites
have the flexibility to provide unique specificity and reactivity for catalytic functions
unknown in nature and may aid in the development of next generation biosensors.