Metalloproteins and Metallopeptides –Natural Metallofoldamers - Metallofoldamers: Supramolecular Architectures from Helicates to Biomimetics - page 29

with only D -form amino acids binds Fe 3þ and folds as the mirror image of the L -form
protein and exhibits the opposite CD spectrum [260]. Moreover, a dramatic conforma-
tional change of unfolded rubredoxin in 5M urea upon metal binding was observed,
wherein the addition of a 100-fold molar excess of Fe 2þ refolded the protein to

90%

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recovery with a t 1/2 of 10ms [261]. In addition to the structures of peptides and proteins

which can be dramatically affected by metal ions to afford various foldameric conforma-
tions, the structures of nucleic acids are also known to be affected by the binding of a
metal center, such as the dramatic conformational change of duplex DNA upon binding
with cisplatin ( cis -diamminodichloroplatinum), a cancer chemotherapeutic agent. Here
the metal center binds a DNA duplex at two N 7 of adjacent guanidine bases or guanidine-
adenine bases in the major groove or two proximal guanidine bases of different strands in
the minor groove, bending the duplex structure by 40-60 along the helix and twisting the
helix by 25-32 [262]. Nucleic acids can also be designed to contain metal-binding bases
to form a metallofoldermers, analogous to the case of designed peptides with a metal-
binding bipyridyl group (Section 1.3.3.2), such as the dramatic conformational change
from a monomeric hairpin structure to a dimeric double-stranded structure for the
sequence 5 0 -TTAATTT-Im-Im-Im-AAATTAA upon Ag þ binding (Figure 1.20) [263].
More detailed discussions about “metallo-DNA” and “metallo-PNA” can be found in this
volume (Chapters 7 and 8). These studies and the several examples described in the above
sections demonstrate the significant flexibility of the backbones of peptides/proteins and
nucleic acids which can adopt various foldameric conformations under different condi-
tions and/or upon metal binding. Future exploration along this direction can be expected
to produce novel metalloproteins, metallopeptides, and metallo-nucleic acids with unique
structures and chemical, physical, and/or biological properties for various applications.

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Figure 1.20 Left: the hairpin structure of a designed nucleic acid with three imidazole-
containing (Im; blue) units as shown on top. Right: the double-stranded helical structure of
this nucleic acid upon Ag þ (pink sphere) binding to bridge the Im pair.