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Growth Hormone Secretagogues: Characterization, Efficacy, and Minimal Bioactive Conformation
Another class of growth hormone (GH) secretagogues has been discovered by altering the backbone structure of a flexible linear GH-releasing peptide (GHRP). In vitro and in vivo characterization confirms these GH secretagogues as the most potent and smallest (Mr< 500) reported. Anabolic efficacy i...
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Published in: | Proceedings of the National Academy of Sciences - PNAS 1995-11, Vol.92 (24), p.11165-11169 |
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container_title | Proceedings of the National Academy of Sciences - PNAS |
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creator | McDowell, Robert S. Elias, Kathleen A. Stanley, Mark S. Burdick, Daniel J. Burnier, John P. Chan, Kathryn S. Fairbrother, Wayne J. Hammonds, R. Glenn Gladys S.Ingle Jacobsen, Neil E. Mortensen, Deborah L. Rawson, Thomas E. Won, Wesley B. Clark, Ross G. Somers, Todd C. |
description | Another class of growth hormone (GH) secretagogues has been discovered by altering the backbone structure of a flexible linear GH-releasing peptide (GHRP). In vitro and in vivo characterization confirms these GH secretagogues as the most potent and smallest (Mr< 500) reported. Anabolic efficacy is demonstrated in rodents with intermittent delivery. A convergent model of the bioactive conformation of GHRPs is developed and is supported by the NMR structure of a highly potent cyclic analog of GHRP-2. The model and functional data provide a logical framework for the further design of low-molecular weight secretagogues and illustrate the utility of an interdisciplinary approach to elucidating potential bound-state conformations of flexible peptide ligands. |
doi_str_mv | 10.1073/pnas.92.24.11165 |
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Glenn ; Gladys S.Ingle ; Jacobsen, Neil E. ; Mortensen, Deborah L. ; Rawson, Thomas E. ; Won, Wesley B. ; Clark, Ross G. ; Somers, Todd C.</creator><creatorcontrib>McDowell, Robert S. ; Elias, Kathleen A. ; Stanley, Mark S. ; Burdick, Daniel J. ; Burnier, John P. ; Chan, Kathryn S. ; Fairbrother, Wayne J. ; Hammonds, R. Glenn ; Gladys S.Ingle ; Jacobsen, Neil E. ; Mortensen, Deborah L. ; Rawson, Thomas E. ; Won, Wesley B. ; Clark, Ross G. ; Somers, Todd C.</creatorcontrib><description>Another class of growth hormone (GH) secretagogues has been discovered by altering the backbone structure of a flexible linear GH-releasing peptide (GHRP). In vitro and in vivo characterization confirms these GH secretagogues as the most potent and smallest (Mr< 500) reported. Anabolic efficacy is demonstrated in rodents with intermittent delivery. A convergent model of the bioactive conformation of GHRPs is developed and is supported by the NMR structure of a highly potent cyclic analog of GHRP-2. The model and functional data provide a logical framework for the further design of low-molecular weight secretagogues and illustrate the utility of an interdisciplinary approach to elucidating potential bound-state conformations of flexible peptide ligands.</description><identifier>ISSN: 0027-8424</identifier><identifier>EISSN: 1091-6490</identifier><identifier>DOI: 10.1073/pnas.92.24.11165</identifier><identifier>PMID: 7479958</identifier><language>eng</language><publisher>United States: National Academy of Sciences of the United States of America</publisher><subject>Amides ; Amino Acid Sequence ; Amino acids ; Anabolics ; Animals ; Biochemistry ; Cell culture techniques ; Consensus Sequence ; Endocrinology ; Female ; Growth Hormone - metabolism ; Growth hormones ; Hormones ; Hormones - chemistry ; Magnetic Resonance Spectroscopy ; Models, Molecular ; Molecular Sequence Data ; Molecules ; Oligopeptides - chemistry ; Peptides, Cyclic - chemistry ; Pituitary Gland, Anterior - metabolism ; Protein Structure, Secondary ; Rats ; Rats, Sprague-Dawley ; Secretion ; Secretory Rate ; Structure-Activity Relationship</subject><ispartof>Proceedings of the National Academy of Sciences - PNAS, 1995-11, Vol.92 (24), p.11165-11169</ispartof><rights>Copyright 1995 The National Academy of Sciences of the United States of America</rights><rights>Copyright National Academy of Sciences Nov 21, 1995</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c525t-7c8dc1206e4347d618cf9d18502cf106b73beef7cad5d6ff3bdc1005fa13865c3</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Uhttp://www.pnas.org/content/92/24.cover.gif</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/2368766$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/2368766$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>230,314,727,780,784,885,27922,27923,53789,53791,58236,58469</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/7479958$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>McDowell, Robert S.</creatorcontrib><creatorcontrib>Elias, Kathleen A.</creatorcontrib><creatorcontrib>Stanley, Mark S.</creatorcontrib><creatorcontrib>Burdick, Daniel J.</creatorcontrib><creatorcontrib>Burnier, John P.</creatorcontrib><creatorcontrib>Chan, Kathryn S.</creatorcontrib><creatorcontrib>Fairbrother, Wayne J.</creatorcontrib><creatorcontrib>Hammonds, R. Glenn</creatorcontrib><creatorcontrib>Gladys S.Ingle</creatorcontrib><creatorcontrib>Jacobsen, Neil E.</creatorcontrib><creatorcontrib>Mortensen, Deborah L.</creatorcontrib><creatorcontrib>Rawson, Thomas E.</creatorcontrib><creatorcontrib>Won, Wesley B.</creatorcontrib><creatorcontrib>Clark, Ross G.</creatorcontrib><creatorcontrib>Somers, Todd C.</creatorcontrib><title>Growth Hormone Secretagogues: Characterization, Efficacy, and Minimal Bioactive Conformation</title><title>Proceedings of the National Academy of Sciences - PNAS</title><addtitle>Proc Natl Acad Sci U S A</addtitle><description>Another class of growth hormone (GH) secretagogues has been discovered by altering the backbone structure of a flexible linear GH-releasing peptide (GHRP). In vitro and in vivo characterization confirms these GH secretagogues as the most potent and smallest (Mr< 500) reported. Anabolic efficacy is demonstrated in rodents with intermittent delivery. A convergent model of the bioactive conformation of GHRPs is developed and is supported by the NMR structure of a highly potent cyclic analog of GHRP-2. 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Anabolic efficacy is demonstrated in rodents with intermittent delivery. A convergent model of the bioactive conformation of GHRPs is developed and is supported by the NMR structure of a highly potent cyclic analog of GHRP-2. The model and functional data provide a logical framework for the further design of low-molecular weight secretagogues and illustrate the utility of an interdisciplinary approach to elucidating potential bound-state conformations of flexible peptide ligands.</abstract><cop>United States</cop><pub>National Academy of Sciences of the United States of America</pub><pmid>7479958</pmid><doi>10.1073/pnas.92.24.11165</doi><tpages>5</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Amides Amino Acid Sequence Amino acids Anabolics Animals Biochemistry Cell culture techniques Consensus Sequence Endocrinology Female Growth Hormone - metabolism Growth hormones Hormones Hormones - chemistry Magnetic Resonance Spectroscopy Models, Molecular Molecular Sequence Data Molecules Oligopeptides - chemistry Peptides, Cyclic - chemistry Pituitary Gland, Anterior - metabolism Protein Structure, Secondary Rats Rats, Sprague-Dawley Secretion Secretory Rate Structure-Activity Relationship |
title | Growth Hormone Secretagogues: Characterization, Efficacy, and Minimal Bioactive Conformation |
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