3.1 Introduction
67
FmocHN
Me
H
OH
O
FmocHN
Ph
OH
O
Fmoc-S 5 (2-Me)
Fmoc-S 5 (2-Ph)
SH
S
R
uv
H
R
+
S
R
S-peptide
R-peptide
Fig. 3.2 A chirality-induced helicity system was used to construct stabilized peptides. The
nonnatural amino acids used were synthesized following previously reported methodology
Fig. 3.3 Inhibition of p53 by MDM2 and MDMX
target p53/MDM2 interactions. However, one potential limitation of these molecules
is that they are all practically inactive against MDMX. Sawyer et al. reported a potent
and selective small molecule, R-5963 that effectively inhibited p53 binding to both
MDM2 and MDMX [24]. However, poor pharmacological characteristics render it
unsuitable for further development. Recently, the use of stapled peptides has provided
a new way to approach these typical PPIs targets, through converting the p53 helix
67
FmocHN
Me
H
OH
O
FmocHN
Ph
OH
O
Fmoc-S 5 (2-Me)
Fmoc-S 5 (2-Ph)
SH
S
R
uv
H
R
+
S
R
S-peptide
R-peptide
Fig. 3.2 A chirality-induced helicity system was used to construct stabilized peptides. The
nonnatural amino acids used were synthesized following previously reported methodology
Fig. 3.3 Inhibition of p53 by MDM2 and MDMX
target p53/MDM2 interactions. However, one potential limitation of these molecules
is that they are all practically inactive against MDMX. Sawyer et al. reported a potent
and selective small molecule, R-5963 that effectively inhibited p53 binding to both
MDM2 and MDMX [24]. However, poor pharmacological characteristics render it
unsuitable for further development. Recently, the use of stapled peptides has provided
a new way to approach these typical PPIs targets, through converting the p53 helix