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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Bibliographic Details
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.
Format: Article
Language:English
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
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Summary: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.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.92.24.11165