Chemistry Reference
In-Depth Information
Fig. 8.10
Protease enzymes mediate many biological processes by specific peptide cleavages.
Silanediol
5
mimics bound intermediate
39
and can inhibit the enzymes
8.4
Silanediol Protease Inhibitors
8.4.1
Design and Activity
Silicon can also be part of a peptide backbone, e.g.
5
, Fig.
8.10
. Silanediols such
as
5
are analogs of a hydrated carbonyl. Silanediols like
36
are stable “hydrates”
because double bonds to silicon (e.g.,
37
) are formed only under extreme or un-
usual circumstances [
38
]. Within a peptide-like structure such as
5
, the silanediol
can masquerade as hydrated amide
39
, an intermediate structure in the hydrolysis
of peptides. Hydrated amide analogs can bind to a protease active site and act as
inhibitors [
39
]. Proteases are a large class of enzymes that mediate a broad spectrum
of biological processes by cleavage of peptide bonds. Important pharmaceutical
applications of protease inhibitors include the treatment of hypertension (by inhibi-
tion of angiotensin-converting enzyme [
40
] and renin [
41
]), cancer (inhibition of
the proteosome [
42
]) and AIDS (inhibition of the HIV protease [
43
]) to name a few
[
44
].
Whereas silanediols are stable toward formation of silanones
37
, their best
known attribute is an alternative dehydration by polymerization, forming siloxanes
(silicones) such as
42
, Fig.
8.11
. In the case of dimethylsilanediol
36
, this polymer-
ization is spontaneous and the product siloxanes are prized for their stability [
45
].
This polymerization, however, is sensitive to the steric environment of the silane.
An outstanding example of this steric effect is diisobutylsilanediol, a liquid crystal-
line material with little tendency to oligomerize [
46
].
