Chemistry Reference
In-Depth Information
Albumin was effectively hydrolyzed by Sal
3
-PAD-Ac, with optimum activity at pH 3 -
just as in the action of pepsin, the most typical aspartic protease. Protease action of
Sal
3
-PAD-Ac at pH 3 appears to involve collaboration of proximal carboxyl groups, in
analogy with pepsin.
Active sites with peptidase activity were also created on polystyrene backbones with
attached metal complexes as the catalytic center. When the Cu(
II
) complex of cyclen
(Cyc) was attached to cross-linked polystyrene, the proteolytic activity of Cu(
II
)Cyc was
enhanced remarkably [49]. By substitution of the chloro groups of PCD with various
nucleophiles, PCD derivatives
9
and
10
were prepared.
-Globulin was hydrolyzed ef-
fectively upon incubation with
9
and
10
. Proteolytic activity of Cu(
II
)Cyc was enhanced
by up to 10
4
-times upon attachment to the polystyrene. Since only a small fraction of
Cu(
II
)Cyc moieties is present on the open surface on PCD and can participate in the
hydrolysis of
c
-globulin, the normalized degree of activation must be substantially
greater than 10
4
-fold. Activation of Cu(
II
)Cyc on the surface of polystyrene was attrib-
uted to the hydrophobic environment.
c
9
10
Since reactive metal centers were secured, attempts were initiated to achieve sub-
strate selectivity in amide hydrolysis by the metal complexes [50, 51]. The active site of
11
was constructed on the surface of partially chloromethylated cross-linked polystyr-
ene (PCPS) by stepwise modification of the polymer [50]. Here, the active site was
chiral since
L
-Arg was used to link the guanidinium group to the polymer. Several
cinnamoyl amide derivatives (
12
-
15
) were tested as substrates for
11
. Neutral amide
12
was not hydrolyzed upon incubation with
11
, but carboxyl-containing amides
13
-
15
were hydrolyzed effectively by
11
, with the optimum activity at pH 9 (Figure 3.9). Also
hydrolyzed by
11
were both acetyl
L-
Phe and acetyl
D-
Phe; a small (1.5) enantioselec-
tivity was observed as the catalyst is chiral.
