Screening methods using G-protein coupled receptors and related compositions
AssigneesThe General Hospital Corporation, Chugai Pharmaceutical Co., Ltd.
InventorsThomas J. Gardella, John T. Potts, Jr., Masaru Shimizu, Fumihiko Ichikawa, Harald Juppner, Makoto Okazaki
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Abstract
The present invention provides screening methods for GPCRs based on the discovery that the affinity of a receptor agonist for a GPCR (such as the parathyroid hormone receptor) when not bound to a G-protein is correlated with the length of time over which the agonist is effective, independently of its pharmacokinetic properties. The invention also provides PTH- and PTHrP-derived polypeptides.
Claims9
A polypeptide of the formula PTH(1-X)/PTHrP(Y-36), or a pharmaceutically acceptable salt thereof, wherein X is an integer between 11 and 18 and Y is X+1, wherein said PTH(1-X) represents the amino acids 1 to X of the human PTH sequence (SEQ ID NO:5) and said PTHrP(Y-36) represents amino acids Y to 36 of the human PTHrP sequence (SEQ ID NO:6), wherein said polypeptide has a high affinity for the R° form of the PTH receptor, and wherein one or more of the following mutations are present in said polypeptide:
- Ala at position 1;
- Ala or Aib at position 3;
- Gln at position 10;
- Arg or homoarginine at position 11;
- Ala at position 12;
- and Trp at position 14.
Dependencies are inferred from the claim text.