Molecular Recognition of Nucleotides - Designing Receptors for the Next Generation of Biosensors - page 63

surface in Fig. 12c ). This way, the competitive influence of the surrounding water
becomes more significant with the consequence that the binding strength is reduced.
Hence, the complex formation between 30 and the phosphate-based substrates is a
good example for the importance of combining different types of non-covalent
interactions within a defined structure in order to achieve selective molecular recog-
nition of biologically relevant targets in aqueous solution.
In conclusion, nucleotide recognition in water has received considerable atten-
tion. Many different artificial host systems have been developed and high binding
constants of up to 10 7 M 1 could be achieved in aqueous media. The majority of
nucleotide receptors are based on polyamines—either cyclic or linear in form.
Another, less frequently used binding motif for ion pairing to the phosphate hinge
is the guanidinium group. Very often aromatic moieties are implemented into the
hosts in order to allow for

-stacking. Following a similar approach, calixarenes or
cyclodextrins are used in order to present hydrophobic pockets for nucleobase and/
or sugar. Another successful principle is the utilization of tweezer receptors which
form a preorganized cavity for accommodation of the substrate. Very often two
anion binding motifs are incorporated—one into each arm. This way the receptors
may adopt a geometry that matches the tetrahedral shape of the phosphate anion.
Hydrogen bonding patterns play a crucial role for the selective recognition of
nucleotides. While strong binding is mainly achieved by increasing charge-charge
interactions, introducing selectivity is more subtle, because purine and, respec-
tively, pyrimidine nucleobases are quite similar in shape and hydrophobicity.
Another aspect of selectivity in almost all artificial host systems is the preference
for tri- over di- and monophosphates, which can easily be explained by the presence
of additional ionic interactions. Peptide-based systems have also been used for the
recognition of nucleotides. Although the results are not yet as good as those seen
with polycationic host systems, the use of amino acids as building blocks offers the
intriguing potential to generate artificial receptors by means of rational approaches,
combinatorial chemistry or combinations thereof.

p

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