Chemistry Reference
In-Depth Information
Fig. 8.8
Preparation of 3-(hydroxydimethylsilyl)alanine
Fig. 8.9
Bioactive peptides incorporating silane amino acids
Incorporation of these β-silyl amino acids into bioactive structures has produced
useful properties. Replacement of a tyrosine in the decapeptide Cetrorelix with
β-(trimethylsilyl)alanine gave
33
[
31
]. Cetrorelix is an antagonist of gonadotropin-
releasing hormone useful in cancer therapy [
36
]. Receptor binding assays using
33
and its carbon analog (containing a
tert
-butyl in place of the trimethylsilyl group)
found them to be potent antagonists. When tested
in vivo
with rats, the silane
33
was found to lower both testosterone and luteinizing hormone levels longer than the
carbon analog [
31
].
Substitution of proline in the angiotensin-converting enzyme (ACE) inhibitor
Captopril with 3-(dimethylsilyl)proline
2
gave
34
, an inhibitor of ACE nearly as
potent as Captopril itself [
37
]. Inhibition of ACE is an important treatment for hy-
pertension.
Insertion of 3-(dimethylsilyl)proline into into a neurotensin analog produced
35
.
This structure retained biological activity and was much more stable toward enzy-
matic degradation than nonsilane congeners [
3
].
A variety of amino acids more remotely substituted with silicon have been pre-
pared and reviews of that work can be found elsewhere [
2
].
