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 (M(r) < 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.
D000595:Amino Acid Sequence; D000818:Animals; D016384:Consensus Sequence; D005260:Female; D013006:Growth Hormone / Q000378:metabolism*; D006728:Hormones / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000737:chemistry*; D010456:Peptides, Cyclic / Q000737:chemistry*; D010903:Pituitary Gland, Anterior / Q000378:metabolism; D017433:Protein Structure, Secondary; D051381:Rats; D017207:Rats, Sprague-Dawley; D012636:Secretory Rate; D013329:Structure-Activity Relationship
D006728:Hormones; D009842:Oligopeptides; D010456:Peptides, Cyclic; D013006:Growth Hormone; C091874:growth hormone-releasing peptide-2