608
Chirality in Biology
a
′′
a
b
c
Ca
′′
a
b
c
pro-
S
pro-
R
O
b
a
′′
a
c
(c)
(d)
(e)
a
O
c
a
′′
b
a
′′
O
c
b
a
(a)
(b)
Fig. 19
Prochirality in Ca
0
a
00
bc. The
different stereoisomeric environments
for a
0
and a
00
are shown as (a) and (b).
(
c
)
=
conventional three-dimensional
representation of cCa
0
a
00
bc.
(
d
)
=
prochirality determination if the
sequence is a
0
>
a
00
>
b
>
c; O
=
eye of
observer. The sequence, a
0
a
00
b,
is left-handed, hence the promoted
group, a
0
,ispro-
S
.
(
e
)
=
Fnal
arrangement.
For that reason, Caabc is often described
as a prochiral structure; it is preferable,
however, to
refer
to
the
situation
as
prostereoisomerism.
A chiral reagent, usually an enzyme, is
able to differentiate between a
0
and a
00
in Ca
0
a
00
bc. This possibility was rational-
ized by Ogston in terms of a three-point
attachment model exactly as for chiral
recognition (at the time of his sugges-
tion, Ogston was unaware of the Eas-
son–Stedman model). It is now apparent
that the three-point attachment model is
a special case and that in the absence of
speci±c constraints (e.g. substrate cannot
approach from the interior of the protein),
eight center interactions are required – a
four-location model.
Stereochemical
descriptors
for
pro-
stereoisomeric ligands derive from an
extension of the Cahn–Ingold–Prelog sys-
tem. One a group, say a
0
, is arbitrarily
assigned a higher priority in the sequence
rule than the other, a
00
. If the ‘‘normal’’
sequence for Caabc is a
>
b
>
c, the ‘‘mod-
i±ed’’ sequence becomes a
0
>
a
00
>
b
>
c.
The model is then viewed in the usual way
fromthesideremotefromthelowestprior-
itygroup
,c
.Ifthesequence
,a
0
a
00
b
is right-handed, the ‘‘promoted’’ group a
0
is assigned the pro-
R
descriptor and a
00
is
assigned the pro-
S
descriptor (Fig. 19c–e).
The descriptors can also be obtained from
projection models, as described previously
for chiral centers. If the two a groups are
hydrogen atoms, the descriptors are writ-
ten as H
R
and H
S
.Aspeci±ccaseconcerns
the two CH
2
COOH groups of citric acid;
the modi±ed sequence is OH
>
COOH
>
C
0
H
2
C
0
OOH
>
C
00
H
2
C
00
OOH and the
descriptors are derived as shown in Fig. 20.
Moreover, in citric acid, each CH
2
group
contains H
R
and H
S
possibilities. In the
important aconitase reaction, it is H
R
of
the pro-
R
methylene group that is removed
along with OH in the formation of
cis
-
aconitate (Fig. 20).
Replacement of H
R
and H
S
, for example,
in CH
3
CH
2
OH, by
2
H leads to the
two enantiomers of [1-
2
H]-ethanol; optical
activity has been demonstrated for
OH
C
2
H
H (
S
)
CH
3
OH
C
H
S
H
R
CH
3
OH
C
H
2
H (
R
)
CH
3
the enantiomers; (
S
)is(
)and(
R
)is(
+
).
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