Easson-Stedman

Stedman Hypothesis
The differences
ferences in biological activity between enantiomers resulted from selective
reactivity of one enantiomer with its receptor. They postulated that such interactions require
requi a
minimum of a three-point
point fit to the receptor. This
Thi is demonstrated in figure for two hypothetical
enantiomers. In figure,, the letters A, B, and C represent hypothetical functional groups that can
interact with complementary sites on the hypothetical receptor surface, represented by A′,
A B′, and
C′. Only one
ne enantiomer is capable of attaining the correct orientation to enable all three
functional groups to fit their respective sites on the receptor surface. The lack of achieving the
same interactions by the other enantiomer explains its reduced biological activity,
a because it is
unable to properly fit into the receptor and, therefore, cannot “trigger” the appropriate
appropr change in
the receptor conformation.
Stedman Hypothesis states that the more potent enantiomer must be involved
The Easson-Stedman
in a minimum of threee intermolecular interactions
interactions with the receptor surface
sur and that the less
potent enantiomer only interacts with two sites. This can be illustrated by looking at the
differences in vasopressor activity of (R)-(–)-epinephrine,
(R) (S)-(+)-epinephrine
epinephrine. With (R)-(–)-
epinephrine, the three points of interaction with the receptor site
te are the substituted aromatic
ring, β-hydroxyl
hydroxyl group, and the protonated secondary ammonium group. All three functional
groups interact with their complementary binding sites on the receptor
ptor surface, producing the
necessary interactions that stimulate the receptor. With (S)
(S)-(+)-epinephrine,
epinephrine, only two interactions
are possible (the protonated secondary ammonium and the substituted aromatic ring). The β-
hydroxyl group occupies the wrong regi
region of space and, therefore, cannot interact properly with
the receptor.