摘要:
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.
摘要:
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.
摘要:
Disclosed are two PTH analog ligands, SP-PTH-AAK and Aib-SP-PTH-AAK, that have long-acting activity at the PTH receptor, as demonstrated both in vitro and in vivo. These polypeptides are thus particularly useful in the treatment of diseases, such as hypoparathyroidism, in which long-acting activity is desired. The method of making the analog polypeptides is also disclosed.
摘要:
Parathyroid hormone(PTH) polypeptide derivatives are disclosed, as are pharmaceutical compositions containing said polypeptides, and synthetic and recombinant methods for producing said polypeptides. Also disclosed are methods for treating mammalian conditions characterized by decreases in bone mass using therapeutically effective pharmaceutical compositions containing said polypeptides. Also disclosed are methods for screening candidate compounds of the invention for antagonistic or agonistic effects on parathyroid hormone receptor action. Also disclosed are diagnostic and therapeutic methods of said compounds.
摘要:
Disclosed are two PTH analog ligands, SP-PTH-AAK and Aib-SP-PTH-AAK, that have long-acting activity at the PTH receptor, as demonstrated both in vitro and in vivo. These polypeptides are thus particularly useful in the treatment of diseases, such as hypoparathyroidism, in which long-acting activity is desired. The method of making the analog polypeptides is also disclosed.
摘要:
The invention provides novel P1R polypeptide antagonists. These antagonists contain amino acid substitutions at selected positions in truncated PTH and PRHrP polypeptides and function by binding selectively to the juxtamembrane (“J”) domain of the receptor. The J domain is the region of the receptor that spans the seven transmembrane domain and the extracellular loops.
摘要:
The present invention is related to synthetic and/or recombinant biologically active peptide derivatives of PTH(1-28). Some of the peptides of the invention are at least 90% identical to a peptide consisting essentially of the amino acid sequence X01ValSerGluIleGlnLeuMetHis AsnLeuGlyLysHisLeuAsnSer MetX02ArgValGluTrpLeuArgLysLysLeu (SEQ ID NO:1), wherein X01 is Ser, Ala or Gly; and X02 is Glu or Arg.
摘要翻译:本发明涉及PTH(1-28)的合成和/或重组生物活性肽衍生物。 本发明的一些肽与基本上由氨基酸序列X01ValSerGluIleGlnLeuMetHis AsnLeuGlyLysHisLeuAsnSer MetX02ArgValGluTrpLeuArgLysLysLeu(SEQ ID NO:1)组成的肽至少90%相同,其中X01是Ser,Ala或Gly; X02是Glu或Arg。
摘要:
Novel parathyroid hormone (PTH) peptides and analogs thereof of the PTH(1–34) fragment are disclosed that combine the N-terminal signaling domain (residues 1–9) and the C-terminal binding domain (residues 15–31) via a linker. Nucleic acid molecules and peptides for PTH(1–9)-(Gly)5-PTH(15–31) (PG5) and PTH(1–9)-(Gly)7-PTH(15–31) and a novel PTH receptor are disclosed. Additionally, methods of screening for PTH agonists, pharmaceutical compositions and methods of treatment are disclosed.
摘要:
The present invention is related to a synthetic and/or recombinant biologically active peptide derivatives of PTH(1-28). Some of the peptides of the invention are at least 90% identical to a peptide consisting essentially of the amino acid sequence X01ValSerGluIleGlnLeuMetHisAsnLeuGlyLysHisLeuAsnSerMetX02ArgValGluTrpLeuArgLysLysLeu (SEQ ID NO:1), wherein X01 is Ser, Ala or Gly; and X02 is Glu or Arg.
摘要翻译:本发明涉及PTH(1-28)的合成和/或重组生物活性肽衍生物。 一些本发明的肽与基本上由氨基酸序列X01ValSerGluIleGlnLeuMetHisAsnLeuGlyLysHisLeuAsnSerMetX02ArgValGluTrpLeuArgLysLysLeu(SEQ ID NO:1)组成的肽至少90%相同,其中X01是Ser,Ala或Gly; X02是Glu或Arg。
摘要:
Novel parathyroid hormone peptide (PTH) and parathyroid hormone related peptide (PTHrP) or derivatives thereof which are biologically active are disclosed, as are pharmaceutical compositions containing said peptides, and synthetic and recombinant methods for producing said peptides. Also disclosed are methods for treating mammalian conditions characterized by decreases in bone mass using therapeutically effective pharmaceutical compositions containing said peptides. Also disclosed are methods for screening candidate compounds of the invention for antagonistic or agonistic effects on parathyroid hormone receptor action. Also disclosed are diagnostic and therapeutic methods of said compounds.