Method for identifying modulators of G protein coupled receptor signaling
AssigneeCaden Biosciences
InventorsAnnette Gilchrist, Heidi M. Hamm
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Abstract
This invention relates to methods for identifying peptides and other compounds which block or enhance G protein coupled receptor mediated signaling with high affinity and specificity and/or which stabilize a particular conformer of a G protein coupled receptor. Assays, methods of treatment and other methods developed in conjunction with these methods also are disclosed.
Claims90
A method of identifying a G protein coupled receptor signaling modifying peptide, which comprises:
- (a) providing a peptide library based on a native G protein coupled receptor binding peptide;
- (b) screening said peptide library for high affinity binding to said G protein coupled receptor;
- and
- (c) selecting a member of said peptide library having binding to said G protein coupled receptor of higher affinity than that of the native peptide.
A method of identifying a G protein coupled receptor signaling modifying compound, which comprises:
- (a) providing a library of candidate compounds to screen for binding to said G protein coupled receptor;
- (b) providing a high affinity G protein coupled receptor binding peptide;
- (c) screening said library of candidate compounds for high affinity binding to said G protein coupled receptor in competition with said high affinity G protein coupled receptor binding peptide;
- and
- (d) identifying a member of said library of candidate compounds having binding to said G protein coupled receptor of equal or higher affinity than that of the peptide of step (b) or a member of said library of candidate compounds binding of which results in increased binding affinity of the peptide of step (b).
A method of inhibiting G protein coupled receptor signaling which comprises contacting a compound with said G protein coupled receptor which interferes with binding of said G protein coupled receptor to its cognate G proteins.
A compound selected from the group consisting of SEQ ID NOS:
- 2, 4, 6, 8, 10, 12, 13, 15, 17, 21, 23, 25-27, 30, 32, 34, 36, 38, 40, 45-85, 94-111, 125-150, 160-164, 175-178 and 183-264.
A method of identifying a G protein coupled receptor signaling enhancer, which comprises:
- (a) providing a peptide library based on a native G protein coupled receptor binding peptide;
- (b) screening said peptide library for high affinity binding to said G protein coupled receptor;
- (c) selecting a member of said peptide library having binding to said G protein coupled receptor of higher affinity than that of the native peptide;
- (d) providing a library of candidate compounds to screen for binding to said G protein coupled receptor;
- (e) screening said library of candidate compounds for high affinity binding to said G protein coupled receptor in competition with a member of said peptide library selected in step (c);
- and
- (f) identifying a member of said library of candidate compounds having binding to said G protein coupled receptor of equal or higher affinity than that of the peptide selected in step (c) or identifying a member of said library of candidate compounds binding of which results in increased binding affinity of the peptide of step (c).
Dependencies are inferred from the claim text.