Chemistry Reference
In-Depth Information
Chapter 8
Bioactive Amino Acids, Peptides
and Peptidomimetics Containing Silicon
Scott McN. Sieburth
8.1
Silicon in Amino Acids and Peptides
More than 50 years have passed since the first silicon-substituted amino acid was
prepared by Birkofer and Ritter, β-trimethylsilyl alanine
1
, Fig.
8.1
[
1
]. Many other
silicon-containing amino acids have been prepared during the intervening years and
these have been broadly investigated [
2
]. Among these interesting non-natural ami-
no acids, an intestively studied analog is sila-proline
2
[
3
]. In contrast, the elusive
amino acid
3
has only been prepared as a derivative of the parent structure and its
limited stability has precluded extensive investigation [
4
]. Substitution on nitrogen,
as in
4
, allows reactions to be performed on peptides [
5
-
7
]. When silicon is part of
a peptide backbone, silanediol
5
, it can mimic a hydrated dipeptide and these have
been studied as inhibitors of protease enzymes. This chapter will focus on structures
related to
1-3
and
5
, including their uses and their syntheses.
8.2
Where Silicon Can—and Cannot—be Used
The introduction of silicon into biologically active molecules has been pursued in
various guises for decades and been the subject of several reviews [
8
-
17
]. There
are no naturally occurring organosilanes. Silane groups can be attached to bioactive
molecules, or silicon can replace carbon within the bioactive structure. Several prin-
ciples are fundamental to the investigation of organosilanes in a biological context:
the oxidative lability of the Si-H bond makes them unsuitable, [
18
] unsaturation
proximal to silicon can lead to instability, [
19
] 3- and 4-membered rings containing
silicon are very strained, [
20
-
22
] multiple bonds to silicon are extremely reactive
