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 G H secretagogues as the most potent and smallest (M(r) < 500) reported. Anabolic efficacy is demonstrated in rodents with intermittent delive ry. A convergent model of the bioactive conformation of GHRPs is devel oped and is supported by the NMR structure of a highly potent cyclic a nalog of GHRP-2. The model and functional data provide a logical frame work 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.