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STD NMR
' U, s1 L, L; K) h+ @$ N+ O0 h, g7 ISTD NMR : K; [ U4 A2 p. V; e# V, f
experiments detect magnetization that is transferred from a receptor protein 1 D* U' \+ w- x1 \
to a bound ligand. Only bound ligands show STD effects. The experiment may be 1 h+ F, G/ y5 O3 [
combined with virtually any other NMR experiment, and therefore is well suitable
3 _/ W3 D7 b5 m# C0 V* _6 _; x) g* _ to tackle even very complex problems. In particular, in combination with multidimensional
8 |. t3 B2 B, A, K# o( B NMR a full characterization of a bound ligand out of a mixture is straightforward.
* T7 {$ G2 J1 E! y1 C) W: z STD NMR is extremely robust and gives maximal effects at protein to ligand ratios
9 @$ {2 W, n9 r7 V4 z greater than ca. 1:100. It follows that less than 1 nmol of protein is necessary
& D4 M( s8 Y2 N" o! S% |$ l for screening. With the availability of so called cryo probes it will be possible
. `* {7 m( p) X. O# e. d to work with hundred pmol amounts of protein. The dissociation constant should $ X6 K7 f' \, L% t
be in the range between nM and mM. Therefore, STD NMR covers at least two orders
8 Z" l. D+ B3 a) k of magnitudes more for dissociation constants than trNOE experiments. From competitive ) B$ m9 L, F) E
STD experiments dissociation constants may be derived. ( ~5 C2 v5 T$ C! V" z

2 p+ Y# a& H ~2 ^% e1 b
! Y& I2 d5 u+ N/ r: @ Schematic
) f( b9 S5 Y d7 q( d$ w" } display of the STD NMR effect. Saturation of the protein leads to a direct saturation ( X; K2 m$ R+ R9 s2 j
of those parts of ligand(s) in direct contact to the protein. By exchange between
9 l% r$ e: y; t. y- g9 \" f bound and free state the saturation is transported to solution and detected * I# S x3 x- K& m7 p
by subtracting a spectrum with saturation from a normal spectrum. 5 Z& E# X- i, j( p# j6 @
STD NMR gives precise information about the binding epitope of the ligand. This
( @% u0 m0 s- T1 w is very important information for the design of a potent drug. The optimal drug 5 {& J9 R4 ?4 L$ p+ F/ C1 }
is of optimal size and optimal shape. The size is deduced from STD NMR, and
X& L! P+ g. `5 |. v k. r2 p8 x the shape is delivered by trNOE experiments.
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