Study summary · research use only
Hypoglycemic action of a novel constrained analog of human growth hormone-(6-13)
Plain-language summary
Paraphrased from the published abstract below — not a verdict on whether anything works.
In this study, the authors developed a stabilized analog of the human growth hormone fragment hGH-(6-13), replacing the hydrolytically vulnerable alpha-aminosuccinimide (Asu11) ring with a gamma-lactam structure to improve stability. They report that in vitro the gamma-lactam11-hGH-(6-13) peptide increased radiolabeled glucose incorporation into glycogen in muscle and conversion to lipid in adipose tissue, and in vivo it enhanced hypoglycemia during intravenous insulin tolerance tests. The authors conclude the analog had biological properties similar to the Asu11 fragment but with improved molecular stability and bioavailability. Species are not specified for the in vivo tests.
Abstract
The amino-terminal region of human GH (hGH), in particular the amino acid sequence Leu-Ser-Arg-Leu-Phe-Asp-Asn-Ala[hGH-(6-13)], has been implicated as a functional region for the regulation of energy metabolism by exerting an insulin-potentiating action on insulin-sensitive tissues. Recent structural studies have revealed that the cyclization of the aspartate (Asp11) residue to form the alpha-aminosuccinimide (Asu11) ring is essential for the biological action of peptides related to this hGH fragment. The pharmacological application of these hGH-(6-13) peptides has been hindered by the vulnerability of the alpha-aminosuccinimide to hydrolytic modification leading to the loss of biological action. We have succeeded in stabilizing the structure of the Asu11-hGH-(6-13) peptide by replacing the alpha-aminosuccinimide ring with compatible and less rapidly metabolized gamma-lactam structures. In the present paper we report the bioactivity profile of an analog of hGH-(6-13) containing a gamma-lactam at residue position 11 that mimics the stereoelectronic and conformational characteristics of the alpha-aminosuccinimide ring. In vitro, the gamma-lactam11-hGH-(6-13) peptide analog increased [14C]glucose incorporation into glycogen in muscles and conversion to lipid in adipose tissues. In vivo, the gamma-lactam11-hGH-(6-13) peptide enhanced hypoglycemia during iv insulin tolerance tests. The results demonstrate that the gamma-lactam11-hGH-(6-13) peptide analog has similar biological properties to the Asu11-hGH-(6-13) peptide fragment, but with improved molecular stability and bioavailability.
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