Chemistry Reference
In-Depth Information
3.2.4
Proximal Group Adducts to Polyethylenimines
Peptide bonds are very stable, having a half-life for spontaneous hydrolysis at pH 7 and
25
8
C of 500-1000 years [33, 34]. Many proteases hydrolyze peptide bonds by using
several organic functional groups such as carboxyl, imidazolyl, hydroxyl, and mercapto
groups as catalytic elements. Examples are aspartic proteases, such as pepsin and HIV
protease, for which the active site contains two aspartic carboxyl groups as the key
catalytic entities for peptide hydrolysis. To synthesize an enzyme-like polymer with
high catalytic activity [35] one needs to design an active site composed of several cat-
alytic groups in close proximity.
Since the 1960s, numerous efforts have been made to design organic catalysts for
the hydrolysis of peptides as models of proteases. In most cases, one could only suc-
ceed in hydrolyzing activated analogues of peptides. The first synthetic organic com-
pound with peptidase activity was obtained by constructing an active site consisting of
three convergent salicylate residues attached to the backbone of polyethylenimine [36].
As illustrated in Eq. 3, three molecules of 4-bromoacetylsalicylate were assembled
around a Fe(
III
) ion and the module was then cross-linked with polyethylenimine
(PEI). Once an amino group of PEI was linked to one of the three salicylates through
a covalent bond, neighboring PEI amino groups, located in the right positions, reacted
with the remaining two salicylates, thereby completing the cross-linkage. After re-
moval of Fe(
III
) by treatment with acid, a water-soluble polymer with sites (Sal
3
), con-
sisting of three proximal salicylates, was obtained.
ð
3
Þ
10
-6
M
)
incubated with (Sal)
3
-PEI (total concentration of (Sal)
3
sites: 4.95
Figure 3.4 Electrophoretic analysis of
c
-globulin (5.35
10
-4
M
) at pH 6.00 and 50
8
C. Numbers indicate the period of incu-
bation. Upper and the lower bands are the heavy and the light chains
of
c
-globulin.
