Biomedical Engineering Reference
In-Depth Information
a
b
O
N
O
30
NH
2
HCl
.
H
2
N
.
HCl
O
NH
HN
O
NH
2
HN
NH
O
O
O
NH
HN
O
NH
HN
N
N
NH
2
H
2
N
O
O
HCl
.
HN
NH
.
HCl
c
Fig. 12 (a) Symmetric tweezer receptor 30;(b) side view of the calculated energy-minimized
structure of the complex between 30 and AMP as obtained from a Monte Carlo conformational
search. Nonpolar hydrogen atoms have been removed for clarity. Color code: substrate (
yellow
),
GCP (
orange
), and receptor backbone (
gray
); (c) solvent-accessible surfaces of 30 (
yellow
) and the
phosphate residue of the nucleotides (
green
). From
left
to
right
: AMP, ADP, and ATP. The
molecular modeling images are reprinted with permission from [
18
]. Copyright 2011 John
Wiley and Sons
headgroup [
18
]. With the help of UV/Vis and fluorescence experiments it could be
shown that 30 forms 1:1 complexes with nucleotides in buffered water (pH 7) with
binding constants of up to
K
10
5
M
1
. Simple phosphates are bound less well, by
one order of magnitude. An even more striking characteristic of this host is that it
prefers to bind to AMP (8
10
4
M
1
) over ADP (3
10
4
M
1
) and ATP
10
3
M
1
)—the monophosphate is bound stronger than the triphosphate by
one order of magnitude. This binding behavior is unusual and so far is unprece-
dented for artificial nucleotide receptors. As described above, the more highly
charged nucleotides are normally preferred due to the formation of additional
charge-charge interactions between receptor and substrate.
According to NMR spectroscopic measurements and molecular modeling studies,
the efficient binding is due to strong electrostatic interactions between the GCP and
lysine groups of the host with the highest charged
(8
-phosphate of the substrates,
a
combined with
interactions within the cavity-shaped receptor. The host and
guest are thus locked in a well-defined complex with specific interactions. The larger
the phosphate hinge on the guest molecule, the more it is located outside of the cavity,
because the receptor cannot wrap around it so effectively (see the solvent accessible
-
p
p
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