The 3D NMR structures o
f six octapeptide agonist analogues o
f somatostatin (SRIF) in the
free
form aredescribed. These analogues, with the basic sequence H-
DPhe/Phe
2-c[Cys
3-Xxx
7-
DTrp
8-Lys
9-Thr
10-Cys
14]-Thr-NH
2 (the numbering re
fers to the position in native SRIF), with Xxx
7 being Ala/Aph, exhibit potentand highly selective binding to human SRIF type 2 (sst
2) receptors. The backbone o
f these sst
2-selectiveanalogues have the usual type-II'
![](/images/gi<font color=)
fchars/beta2.gi
f" BORDER=0 ALIGN="middle">-turn reported in the literature
for sst
2/3/5-subtype-selective analogues.Correlating the biological results and NMR studies led to the identi
fication o
f the side chains o
f DPhe
2,
DTrp
8, and Lys
9 as the necessary components o
f the sst
2 pharmacophore. This is the
first study to show thatthe aromatic ring at position 7 (Phe
7) is not critical
for sst
2 binding and that it plays an important role in sst
3and sst
5 binding. This pharmacophore is, there
fore, di
fferent
from that proposed by others
for sst
2/3/5 analogues.