Merck + Co., Inc.

David L Linemeyer

Kenneth A Thomas, Jr

John W Hess

Joseph A Borkowski

John G Menke

Kathleen K Bierilo

Douglas J MacNeil

Catherine D Strader

Carina P Tan

Margaret A Cascieri

David H Weinberg

Lin-Lin Shiao

Kenneth A Thomas

E Tracy Jones

Gregory L Helms

Wendy S Horn

Guillermo Gimenez-Gallego

Linda J Kelly

DNAs encoding bradykinin B,receptors from mammalian cells have been cloned and characterized. The recombinant receptor is capable of forming receptors which bind desArg,kallidin and other B,-specific ligands. The DNA has been expressed in recombinant host cells which produce active recombinant protein. In addition, the recombinant host cells are utilized to establish a method for identifying modulators of the receptor activity, and receptor modulators are identified.

Bradykinin B1 receptor antibodies

DNAs encoding bradykinin B.sub.1 receptors from mammalian cells have been cloned and characterized. The recombinant receptor is capable of forming receptors which bind des-Arg.sup.10 kallidin and other B.sub.1 -specific ligands. The DNA has been expressed in recombinant host cells which produce active recombinant protein. In addition, the recombinant host cells are utilized to establish a method for identifying modulators of the receptor activity, and receptor modulators are identified.

Purified bradykinin B.sub.1 receptor

Neuropeptide Y receptor

DNA encoding bradykinin B1 receptor

A novel mammalian neuropeptide Y receptor and method of making the receptor are provided. The invention includes DNA encoding the receptor, the receptor, assays employing the receptor, cells expressing the receptor, antibodies which bind specifically to the receptor, RNA encoded by the DNA sequence or its complementary sequence, and single-stranded DNA with a sequence complementary to the RNA which encodes the receptor. The receptor and assays employing the receptor are useful for identifying compounds which bind to the receptor, including specific modulators of the receptor. Such compounds are useful for treating a variety of disease conditions, including obesity, diabetes, anxiety, hypertension, cocaine withdrawal, congestive heart failure, memory enhancement, cardiac and cerebral vasospasm, pheochromocytoma and ganglioneuroblastoma, and Huntington's, Alzheimer's and Parkinson's diseases.

Mutant human acidic fibroblast growth factor proteins are recombinantly produced having replaced cysteine residues with amino acids incapable of disulfide bond formation. The recombinantly produced mutant human acidic fibroblast growth factor proteins have improved biological activity in the absence of heparin when compared to wild-type recombinant human acidic fibroblast growth factor.

Cysteine-modified acidic fibroblast growth factor and methods of use

Acidic fibroblast growth factor (aFGF) is isolated and purified from human brain tissue. The distinctive and complete amino acid sequences of both bovine and human aFGFs are determined and herein disclosed. Unique genes coding for these disclosed amino acid sequences are constructed. The bovine gene is derived from reverse translation of the aFGF amino acid sequence with unique restriction sites included while the human gene is derived by specific point mutations of the bovine gene. Each gene construct is inserted into an expression vector which is used to transform an appropriate host. The transformed host cells produce recombinant aFGF (r-aFGF), human or bovine, which is purified and has activity equivalent to the native protein. Both recombinant and purified brain-derived human and bovine aFGF are active mitogens for mesoderm and neuroectoderm-derived cells in culture, and promote wound healing of soft tissue, cartilaginous tissue and musculo-skeletal tissue. Acidic fibroblast growth factor, recombinant and purified brain-derived, is also useful for the growth of vascular endothelial cells and for coverage of polymeric vascular grafts; growth of such cultures on tubular supports for production of blood vessles for implantation; and stimulation or facilitation of blood vessel growth and repair in vivo.

Brain derived and recombinant acidic fibroblast growth factor

Cysteine-modified acidic fibroblast growth factor

This invention relates to compounds of structural formula (I) ##STR1## which are useful as Cholestrol lowering agents.

Cholesterol lowering agents

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Westfield, NJ, United States of America

David L Linemeyer