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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
Main Authors: 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.
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container_end_page 11169
container_issue 24
container_start_page 11165
container_title Proceedings of the National Academy of Sciences - PNAS
container_volume 92
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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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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