Download ppt

32 amino acids is a critical length
rDNA origin
synthetic
recombinant
The mean bioavailability of Calcitonin-Salmon Nasal Spray is
approximately 3% of that of injectable calcitonin in normal subjects.
Human calcitonin :
1 disulfide
bridge
Not N-glycosylated
32
prolineamide
modified C-terminus !
Why is salmon calcitonin more potent than human calcitonin ?
The conformation hypothesis seems the most likely
.
Calcitonin :
salmon
human
Ser
Asn
Val
Lys Leu Ser
Glu Leu His
Leu Gln
Tyr
Thr
Arg
Ser
Identity : 16 aa / 32 aa
Thr
Comparison human / salmon calcitonin
(amino acids sequence)
salmon:
Cys-Ser-Asn-Leu-Ser-Thr-Cys-Val-Leu-Gly-Lys-Leu-Ser-Gln-GluLeu-His-Lys-Leu-Gln-Thr-Tyr-Pro-Arg-Thr-Asn-Thr-Gly-Ser-GlyThr-Pro
human:
Cys-Gly-Asn-Leu-Ser-Thr-Cys-Met-Leu-Gly-Thr-Tyr-Thr-Gln-Asp
-Phe-Asn-Lys-Phe-His-Thr-Phe-Pro-Gln-Thr-Ala-Ile-Gly-Val-GlyAla-Pro
Osteoporosis
Young 2013 EPFL student
50% bone mass loss
after menopausis
nomal
osteopenia
osteoporosis
Osteoporosis
decreased bone density
1
5
Lumbar vertebrae : the last 5
Hoefnagel
osteoporosis
L2 : 2nd lumbar vertebra
Vertebrae of 40- vs. 92-year-old
women
Note the marked loss of trabeculae with preservation of cortex.
2 problems linked to osteoporosis :
- vertebral compression fracture
- hip fracture
Densitometry
measuring bone density
Bilateral ovaryectomy (OVX) in goats  osteoporosis
Large animal
models can be
investigated
using the same
instruments as
for humans.
BMD : Bone Mass Density
OVX induces bone mass loss confirming the link between
menoposis and osteoporosis
prevention
CALCITONIN
no effect
2 major risks
of osteoporosis :
vertebral fracture
hip fracture
Administration routes for recombinant proteins.
injecteur
projecteur
(sans aiguille)
nasal spray
Oxytocyn : CYIQNCPLG
9 amino acids
modified C-terminus !
Syntocinon nasal spray :
medical use : lactation help
published in 2009
These 4 administration routes are nonsense
Human growth hormone : 191 aa.
Progress in DNA synthesis :
Chemical DNA synthesis:
Synthétiseur automatique d’ADN: