Chemistry Reference
In-Depth Information
11.1 Introduction
Biomimetic oligomers are synthetic molecules akin to natural biopolymers, namely pep-
tides, proteins and oligonucleotides. Both natural biopolymers and their artificial mimics
are sequence-specific oligomers capable of folding into well defined three-dimensional
structures in solution. One difference between them, however, is the identity of their back-
bone: while peptides and proteins are composed of a-amino acids, biomimetic oligomers
are assembled from non-natural monomers. There are mainly two groups of biomimtic
oligomers: single-stranded (peptidomimetics and their abiotic analogues) and self-
assembled multiple-stranded (nucleotidomimetics and their abiotic analogues). As the
mimics of oligonucleotides that bind metal ions were discussed in the previous two chap-
ters, the folding behavior of single-stranded biomimetic oligomers upon metal binding is
the focus of this chapter. Such abiotic oligomers were the subject of numerous studies in
recent years, and their synthesis, characterization and folding behavior were investigated.
This research revealed that, similar to natural biopolymers, the conformation of folded
biomimetic oligomers (“biomimetic foldamers”) could be controlled by a variety of strat-
egies involving non-covalent interactions [1]. These include the use of specific non-
covalent forces, such as hydrogen bonding, donor-acceptor complexation, aromatic
p-stacking and metal-ligand interactions, as well as non-specific van der Waals interac-
tions and solvophobic effects [1-5].
Among these interactions, metal-ligand coordination represents an exciting opportu-
nity to gain structure stability in a selective manner; as proteins often select a specific
metal from the pool of metal ions that are present in the cellular environment, biomimetic
oligomers can be designed to fold upon binding to a particular metal ion. It is now well
established that the identity of the metal-binding ligands and their coordination mode, as
well as side chain interactions, have a crucial role in governing metal binding and selec-
tivity in proteins. The selective affinity of a protein to a specific metal ion determines its
final three-dimensional structure, which eventually leads to the metalloprotein's unique
function. Despite the well known relationship between the structure and function of met-
alloproteins, the association between metal coordination and protein folding, including
the contribution of metal sites to structural stability, is still, in most cases, poorly under-
stood. In addition, it is also not quite clear whether metal-binding sites in proteins are
generally rigid or flexible, how well the protein can adjust to the coordination constraints
of the incoming metal ion, or, on the contrary, whether the metal ion can obey the require-
ments of the protein matrix. Thus, the incentive behind the generation of synthetic single-
stranded biomimetic metallofoldamers is twofold. First, producing biomimetic oligomers
which incorporate metal-binding ligands varying in their type, their coordination capabili-
ties and their position along the oligomer spine should enable a detailed investigation of
the oligomer folding behavior upon metal complexation. This will shed light on the corre-
lation between metal binding, folding and structure stability. Second, the new biomimetic
metallofoldamers are anticipated to encompass unique functions, such as selective cataly-
sis and sensing. If a biomimetic oligomer could fold upon the selective binding of one
metal ion in the presence of other metals, for example, detection of the folding event will
serve as a sensor for this specific metal.
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