Biomedical Engineering Reference
In-Depth Information
tumor suppressor functions described for KLK3/PSA at several levels.
25
Our
better understanding of the dual roles of KLK3/PSA in prostate-cancer
development and progression will greatly help dissect the stages and prostate-
tumor subtypes that will benefit from compounds that activate KLK3/PSA
from those that would benefit from the use of KLK3/PSA inhibitors.
Phage display was also applied to the identification of novel peptide acti-
vators of KLK3 activity.
84
Initially, the B2 cyclic peptide (9.2) was selected.
Based on B2, new peptides were produced, carrying replacements of the dis-
ulfide bond. Of these, 9.3 was found to stimulate the activity of KLK3/PSA. In
designing such replacements, it is important to maintain the length of the S-S
bridge (shaded region in Figure 9.2) to achieve maximum stimulation of the
KLK3/PSA activity. The advantage of these replacements lies in their higher
OH
O
O
H
2
N
N
O
O
H
NH
NH
HN
OH
O
NH
O
O
OH
HN
O
O
O
HN
NH
O
O
NH
2
H
NH
HN
S
S
O
O
9.2
O
OH
O
N
N
O
N
N
H
H
O
O
9.3
O
HO
Figure 9.2
Peptide activators of KLKs.
