Biomedical Engineering Reference
In-Depth Information
a
S
Y
L
Y
1
S
F
1
M
C
S
C
K
C
T
C
ET-1
ET-3
D
D
21
21
K
K
E
E
C
V
Y
F
C
H
L
D
I
I
W
C
V
Y
Y
C
H
L
D
I
I
W
S
D
W
M
S
K
1
1
L
C
S
C
T
C
S
C
ET-2
S6b
D
D
K
21
K
21
E
E
C
V
Y
F
C
H
L
D
I
I
W
C
L
Y
F
C
H
Q
D
Y
I
W
b
1
21
[Ala1,3,11,15]ET-1
A
S A
S
S
L
M
D
K
E
A
V
Y
F
A
H
L
D
I
I
W
1
16
BQ-3020
Ac-
L
M
D
K
E
A
V
Y
F
A
H
L
D
I
I
W
1
14
IRL-1620
Suc-
D
E
E
A
V
Y
F
A
H
L
D
I
I
W
1
S
C
C
V
IRL-1038
13
Y
BQ-788
F
C
H
L
D
I
I
W
IRL-2500
A-192621
Ro 46-8443
c
RES-701-1
1
N
W
G
9
16
H
D
W
F
F N
Y
Y
W
G
P
T
A
Fig. 3.1
ETs and selective antagonists of the ET
B
receptor.
a
Primary structures of ET-1, ET-2,
ET-3 and related sarafotoxin b (S6b; adapted from Fagan et al.
2001
).
b
Selective antagonists of
the ET
B
receptor (adapted from Mazzuca and Khalil
2012
). The amino acids conserved between
ET-1, ET-2 and ET-3 are coloured in
green
. The residues proposed to constitute the pharmacophore
of ET-1 are circled in
bold
. The amino acids different from those of ET-1 are shown in
yellow
.
c
Primary and secondary structures of RES-701-1. (The latter has been kindly provided by Tomoaki
Kuwaki, Kyowa Hakko Kirin Company; Katahira et al.
1995
)
the ET
A
receptor, mainly produced in vascular smooth muscle cells, mediates va-
soconstriction and cell proliferation, while the ET
B
receptor, mainly produced by
endothelial cells, mediates vasodilatation and ET-1 clearance (Mazzuca and Khalil
2012
; Ohkita et al.
2012
).
The general structure of ETs contains a cystine-stabilized α-helix motif in the
N-terminal region of the 21-residue sequence, which consists of a β-turn fol-
lowed by an α-helix (Tamaoki et al.
1991
; Takashima et al.
2004a
). Comparison
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