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STD NMR 7 b6 O E l4 ^$ z( w) v" F
STD NMR
0 D0 h) n; M) h& x experiments detect magnetization that is transferred from a receptor protein , E5 n N* }+ T" X4 F) D& ^
to a bound ligand. Only bound ligands show STD effects. The experiment may be + F$ }$ h; U$ E3 z3 Q& j, B
combined with virtually any other NMR experiment, and therefore is well suitable
8 d0 D2 D6 k* }1 j5 v to tackle even very complex problems. In particular, in combination with multidimensional 9 C* {" `. k6 E2 @
NMR a full characterization of a bound ligand out of a mixture is straightforward.
|! b( \7 \. E9 W2 C STD NMR is extremely robust and gives maximal effects at protein to ligand ratios
3 e, N$ z& q7 P2 I greater than ca. 1:100. It follows that less than 1 nmol of protein is necessary $ Z) i- s$ M8 l6 Z; ~
for screening. With the availability of so called cryo probes it will be possible 7 M1 D$ x" ~7 f, h6 e. \
to work with hundred pmol amounts of protein. The dissociation constant should # V8 J! ~$ O8 ]
be in the range between nM and mM. Therefore, STD NMR covers at least two orders
. Y5 q6 H! ?# F5 z* [+ ^ of magnitudes more for dissociation constants than trNOE experiments. From competitive
" i& f* `( h4 O2 x7 |9 L STD experiments dissociation constants may be derived. & g7 l4 f& p; w. i

3 M# ]% V1 f" E8 |0 W! S
0 Y# a, R4 ~* P Schematic
/ ~% z+ x/ w2 h% H5 p* U ` display of the STD NMR effect. Saturation of the protein leads to a direct saturation * X M9 P8 I( ?8 ]. u5 L- x
of those parts of ligand(s) in direct contact to the protein. By exchange between
8 K( K# a+ Z8 h$ V: [ bound and free state the saturation is transported to solution and detected # H, u( u2 y% F# @. a! ^
by subtracting a spectrum with saturation from a normal spectrum.
: Y0 p( K( J. | STD NMR gives precise information about the binding epitope of the ligand. This
1 y- ^0 M2 U7 q3 C, C: C3 D& a* N is very important information for the design of a potent drug. The optimal drug
* `8 t X+ [' a3 E. |9 L* Z7 y is of optimal size and optimal shape. The size is deduced from STD NMR, and
6 e' s' O$ O* j9 Q# {8 ~. ^; W the shape is delivered by trNOE experiments.
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