Chemistry Reference
In-Depth Information
Fig. 6 Glycan structures present on recombinant hCG (determined from Amoresano
et al.,
25
and Gervais et al.
71
).
the testes. The components found in Pregnyl
s
(Merck), Follutein
s
(Bristol-Myers Squibb), Profasi
s
(Merck Serono) and Choragon
s
/
Novarel
s
(Ferring Pharmaceuticals) are extracted from pregnant urine.
In Ovidrel
s
/Ovitrelle
s
(Merck Serono), hCG is produced by DNA re-
combinant technology in CHO cells. Often hCG medication is used as an
LH substitute because it binds to the LH/hCG receptor.
N-Glycans of recombinant hCG (rhCG) produced in CHO cells were
also characterized by mass spectrometry and showed that the re-
combinant hormone mainly bears complex biantennary structures with a
variable level of sialylation and fucosylation and minor tri- and tetra-
antennary structures (Fig. 6).
25,71
The O-glycans structures are hetero-
geneous as represented in Table 3.
25,71,94
5 Bioactivity of gonadotropins
The overall in vivo activity of the gonadotropins is dependent upon key
parameters: (i) their clearance rate from circulation, (ii) their ability to
bind their target receptor and (iii) their ability to induce an ecient
transduction signal. Each of them is physiologically related to different
glycosylation states.
41
Terminal sialic acid and GalNAc-sulfate modulate
serum half-life of gonadotropins in opposite fashion as liver GalNAc
sulfate receptors take up circulating LH to sustain pulsatility
96
while
sialic acid prevents uptake all the gonadotropins by receptors specific to
asialoglycoproteins,
95
thereby, allowing prolonged duration of the hor-
mone in blood.
5.1 FSH
Site-directed mutagenesis was used to disrupt each glycosylation site in
FSH independently but the data remain controversial. While some
authors observed an increased receptor binding for each mutant,
97
others described an increase in receptor binding only after a-Asn78
mutation
98
and/or a-Asn52 mutation but a decrease binding for mutated
b-Asn3
5
and no effect for other glycosylation site.
99
In contrast, all the
studies agree on the important role of a-Asn52 in in vitro bioactivity.
97-99
Interestingly all carbohydrate residues significantly affect the metabolic
Search WWH ::
Custom Search