Document 13482289

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Diagram of IGF-I Ribbon Structure removed due to copyright considerations. See Figure 1 in Vajdos, F. F., et. al. "Crystal Structure
of Human Insulin-like Growth Factor-1: Detergent Binding Inhibits Binding Protein Interactions." Biochemistry 40, no. 37 (2001).
IGF-1 Analog
T
G
N-terminus
Q
A +R +R
P
I
A
D
T
E
L
6
C
D
47
C
C
C 52
48
70
L +
R
S
Q
+K
N
F
V
C
C
F
L
61
Y
L
P
+K
E
A
T
+K
P
E
D
G
A
M
V
G
Y
L
S
A
L
S
+R
F +R
G
S
C-terminus
V
missing
S
A
G
Y
P
F
D
+R
G
18
D = Asp
E = Glu
COOH
K = Lys
R = Arg
NH+3
( +)
COO + H+
( )
NH2 + H+
pK ~ 4
pK ~ 10.5 -12.5
Figure by MIT OCW.
(9)
(-)
(9)
(+)
Downstream Conc./ Upstream Conc., %
100nM IGF-I
2
1.5
100nM IGF-I
1
0.5
<1nM 125I-IGF-I
added upstream
0
τ lag = 267min
0
400
800 1200 1600 2000
TIME, minutes
IGF
ACTIVITY, CPM
3×106
2×106
F
106
B
0
0
20
40
60
80
FRACTION NUMBER
100
Binding of Insulin-Like Growth Factor-1 (IGF-1)
to IGF Binding Proteins in Extracellular Matrix
(NOT CELL SURFACE RECEPTORS)
125
I-IGF-1 Tissue/1251-IGF-1 Bath
12
10
8
6
4
2
0
No cold
0.1
1
10
25
50
100
200
Unlabeled IGF-1 (nM)
Measurement: Competition of Unlabeled IGF with
125
I-IGF-1 to Binding Proteins in ECM
Figure by MIT OCW.
After Figure 2A in Bhakta, N. R., et. al. "The Insulin-like Growth Factors (IGFs)
I and II Bind to Articular Cartilage via the IGF-binding Proteins." J Biol Chem 275, no. 8 (2000).
Figure removed due to copyright considerations. See Figure 1 in Garcia, A. M., et. al. "Transport and Binding of Insulin-like Growth
Factor I through Articular Cartilage." Archives of Biochemistry and Biophysics 415, no. 1 ( July 1, 2003): 69-79.
Figure removed due to copyright considerations. See Figure 2
in Garcia, A. M., et. al. "Transport and Binding of Insulin-like Growth
Factor I through Articular Cartilage." Archives of Biochemistry and
Biophysics 415, no. 1 ( July 1, 2003): 69-79.
125
2.5
tau
lag
2
= 230 min
D = 2.2 x 10−7 cm2/s
15nM IGF−I
1.5
Downstream
125
I−IGF−I (% of total)
I−IGF−I Transport Kinetics
75nM Analog
Steady Flux
1
Lag Time (tau
)
lag
0.5
Calibration
200
400
600
800
1000
1200
Time (min)
1400
1600
1800
2000
Figure removed due to copyright considerations. See Figure 3B in Garcia, A. M., et. al. "Transport and Binding of Insulin-like Growth
Factor I through Articular Cartilage." Archives of Biochemistry and Biophysics 415, no. 1 ( July 1, 2003): 69-79.
NORMALIZED CONCENTRATION
150
100
Theory
50
0
-50
-50
0
50
100
NORMALIZED TIME, t/τ
150
Figure removed due to copyright considerations. See Figure 5 in Garcia, A. M., et. al. "Transport and Binding of Insulin-like Growth
Factor I through Articular Cartilage." Archives of Biochemistry and Biophysics 415, no. 1 ( July 1, 2003): 69-79.
Figure removed due to copyright considerations. See Figure 4 in Garcia, A. M., et. al. "Transport and Binding of Insulin-like Growth
Factor I through Articular Cartilage." Archives of Biochemistry and Biophysics 415, no. 1 ( July 1, 2003): 69-79.
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