Biology Reference
In-Depth Information
Fig. 8.7
Specifi c amino acid changes create antagonism. Graphs showing both intrinsic IP release
(
light grey
) and antagonism of KP-10 stimulated IP release (
dark grey
). IP is the concentration at
which stimulation reached 50% of the maximal (EC
50
) and Ant is the percentage for maximal antag-
onism at micromolar doses. (
a
) Substitution of Ser
5
with Gly enhances antagonism at high doses but
still activates the receptor at 45 nM. (
b
) Additional substitution at position 6 also stimulates IP
release but D -Phe
6
does not increase the antagonism over peptide 208. (
c
) Addition of D- Trp 8
increases antagonism to 69% with an IC
50
of 1 nM. (
d
) Substitution of Gly
5
with a bulky D -Trp
5
reduces this antagonism to 50% suggesting a small fl exible amino acid is needed at position 5.
(
e
) Adding D-Ala at position 1 of 228 increases antagonism to 93% with and IC
50
of 70 nM and no
intrinsic IP production. (
f
) Adding D-Asn at position 2 of 228 decreases antagonism as does (
g
) add-
ing D-Trp at position 3. (
h
) Removal of D -Trp
8
from peptide 234 completely ablates antagonism
changes at position 2; D -Asn
2
(peptide 232) and D -Ala
2
(peptide 236) did not
increase the antagonistic effects over peptide 228. Therefore substitution of this
residue does not appear important for antagonism of the receptor. Finally, substitu-
tions of position 3 to D -Trp
3
(peptide 231) or D -Ala
3
(peptide 235) also had no fur-
Search WWH ::
Custom Search