Selecting ligand agonists and antagonists

PCT No. PCT/US92/03743 Sec. 371 Date Sep. 29, 1993 Sec. 102(e) Date Sep. 29, 1993 PCT Filed May 6, 1992 PCT Pub. No. WO92/21029 PCT Pub. Date Nov. 26, 1992.We have discovered that growth hormones form ternary complexes with their receptors in which site 1 on the hormone first binds to one molecule o...

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Hauptverfasser:	MULKERRIN, MICHAEL G, ULTSCH, MARK, WELLS, JAMES A, CUNNINGHAM, BRIAN C, DEVOS, ABRAHAM M
Format:	Patent
Sprache:	eng
Schlagworte:	AGRICULTURE ANIMAL HUSBANDRY BEER BIOCHEMISTRY CARE OF BIRDS, FISHES, INSECTS CHEMISTRY COMPOSITIONS THEREOF CULTURE MEDIA ENZYMOLOGY FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIREDCHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERSFROM A RACEMIC MIXTURE FISHING FORESTRY HUMAN NECESSITIES HUNTING HYGIENE INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIRCHEMICAL OR PHYSICAL PROPERTIES MEASURING MEDICAL OR VETERINARY SCIENCE METALLURGY MICROBIOLOGY MICROORGANISMS OR ENZYMES MUTATION OR GENETIC ENGINEERING NEW BREEDS OF ANIMALS ORGANIC CHEMISTRY PEPTIDES PHYSICS PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES PROPAGATING, PRESERVING OR MAINTAINING MICROORGANISMS REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS ORMEDICINAL PREPARATIONS SPIRITS TESTING TRAPPING VINEGAR WINE
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Zusammenfassung:	PCT No. PCT/US92/03743 Sec. 371 Date Sep. 29, 1993 Sec. 102(e) Date Sep. 29, 1993 PCT Filed May 6, 1992 PCT Pub. No. WO92/21029 PCT Pub. Date Nov. 26, 1992.We have discovered that growth hormones form ternary complexes with their receptors in which site 1 on the hormone first binds to one molecule of receptor and then hormone site 2 then binds to another molecule of receptor, thereby producing a 1:2 complex. We believe this phenomenon is shared by other ligands having similar conformational structure. Assays based on this phenomenon are useful for identifying ligand agonists and antagonists. Sites 1 and 2 are structurally identified to facilitate generation of amino acid sequence variants of ternary complex-forming ligands. Novel variants of growth hormone, prolactin placental lactogen and other related ligands are provided. As a result of our studies with the ternary complex we have determined that selected antibodies to the receptor for these ligands are capable of acting as ligand agonists or antagonists. Novel growth hormones and novel uses for anti-growth hormone receptor antibodies are described.