{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T16:35:53Z","timestamp":1773419753282,"version":"3.50.1"},"reference-count":28,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[1997,8,1]],"date-time":"1997-08-01T00:00:00Z","timestamp":870393600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[1997,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Human parathyroid hormone (hPTH)-(1\u201331)NH2 (Ostabolin), which only stimulates adenylyl cyclase (AC) instead of AC and phospholipase-C as do hPTH(1\u201384) and hPTH(1\u201334), strongly stimulates femoral cortical and trabecular bone growth in ovariectomized (OVX) rats. Two side-chain lactams have been introduced in the hydrophilic face of the receptor-binding region of the fragment's Ser17-Val31 amphiphilic \u03b1-helix in an attempt to develop improved analogs for the treatment of osteoporosis. Replacing the polar Lys27 with an apolar Leu on the hydrophobic face of this \u03b1-helix and stabilizing the helix with a lactam between Glu22 and Lys26 produced a fragment, [Leu27]-cyclo(Glu22-Lys26)-hPTH(1\u201331)NH2, which had six times the AC-stimulating ability of hPTH(1\u201331)NH2 in ROS 17\/2 rat osteosarcoma cells, but the other helix-stabilizing lactam derivative [Leu27]-cyclo(Lys26-Arg30)-hPTH(1\u201331)NH2 did not have a greater AC-stimulating ability than hPTH(1\u201331)NH2, to stimulate AC in ROS 17\/2 rat osteosarcoma cells. As expected from AC stimulation being responsible for PTH's anabolic action, [Leu27]-cyclo(Glu22-Lys26)-hPTH(1\u201331)NH2 was, depending on the experimental design, a 1.4 to 2 times better stimulator of trabecular bone growth in the OVX rat model than either hPTH(1\u201331)NH2 or [Leu27]-cyclo(Lys26-Arg30)-hPTH(1\u201331)NH2. Thus, there is now a more potently anabolic derivative of hPTH(1\u201331)NH2, [Leu27]-cyclo(Glu22-Lys26)-hPTH(1\u201331)NH2, which might ultimately prove to be one of the more effective therapeutics for osteoporosis.<\/jats:p>","DOI":"10.1359\/jbmr.1997.12.8.1246","type":"journal-article","created":{"date-parts":[[2006,4,26]],"date-time":"2006-04-26T22:45:06Z","timestamp":1146091506000},"page":"1246-1252","source":"Crossref","is-referenced-by-count":35,"title":["Cyclization by a Specific Lactam Increases the Ability of Human Parathyroid Hormone (hPTH)-(1\u201331)NH2 to Stimulate Bone Growth in Ovariectomized Rats"],"prefix":"10.1093","volume":"12","author":[{"given":"J. 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