Design, synthesis, and biological activity of peptides which release growth hormone in vitro

Endocrinology
F A MomanyK Newlander

Abstract

Experimental observations showed that the analogs [D-Trp2]- and [D-Phe2]methionine enkephalin amide were weakly active in releasing GH from rat pituitary in vitro. These observations were used to design more active GH-releasing factors. Conformational energy calculations were carried out, and energetically favored conformations of these polypeptides were found. Structural similarities as well as structural differences between active and inactive analogs were examined, and new sequences were predicted. Progressively more active analogs were designed, then synthesized, and tested. This cycle of steps was repeated, each time using structural and chemical concepts as design guides, until a series of very active analogs resulted. The most active analog to date, Tyr-D-Trp-Ala-Trp-D-Phe-NH2, was shown to release GH in vitro at 10-30 ng/ml medium, which is approximately 10(3) times more active than the two starting enkephalin-based analogs. From the structure-activity data, a mechanism for binding at the receptors is formulated, and a comparison is made between the structural relationships of the GH-releasing peptide analogs and the GH inhibitor, somatostatin.

Citations

Apr 1, 1991·Fish Physiology and Biochemistry·C F Chang, S J Lin
May 29, 2007·Pituitary·Chrysanthia A LeontiouMárta Korbonits
Feb 23, 2011·Reviews in Endocrine & Metabolic Disorders·Chung Thong LimMárta Korbonits
Mar 1, 1995·Trends in Endocrinology and Metabolism : TEM·M Korbonits, A B Grossman
Nov 5, 2003·Frontiers in Neuroendocrinology·Massimo ScacchiFrancesco Cavagnini
Mar 14, 2002·Regulatory Peptides·Guiyun WangGeorge H Greeley
Jul 12, 2000·European Journal of Medicinal Chemistry·M AnkersenB Sehested Hansen
Jan 1, 1999·Bioorganic & Medicinal Chemistry Letters·L YangA A Patchett
May 14, 1999·Trends in Endocrinology and Metabolism : TEM·R G SmithA Howard
Jul 18, 1995·Proceedings of the National Academy of Sciences of the United States of America·A A PatchettG Hickey
Nov 21, 1995·Proceedings of the National Academy of Sciences of the United States of America·R S McDowellT C Somers
Feb 21, 2009·Human Reproduction Update·Giuseppe FanciulliGiuseppe Delitala
Nov 1, 1995·Clinical Endocrinology·A F MassoudC G Brook
Mar 8, 2008·Endocrine Journal·Simoni A KatergariNikos K Nikolettos
Jul 1, 1993·The Journal of Pediatric Endocrinology·P MartulC Dieguez
Oct 1, 1995·Journal of Pediatric Endocrinology & Metabolism : JPEM·R DeghenghiV Locatelli
Sep 1, 1996·Journal of Pediatric Endocrinology & Metabolism : JPEM·S DamjanovićF F Casanueva
Aug 27, 2004·Proceedings of the National Academy of Sciences of the United States of America·Steffen HelmlingSven Klussmann
Apr 9, 2004·Proceedings of the National Academy of Sciences of the United States of America·Yuxiang SunRoy G Smith
Jun 8, 2014·Journal of Pharmaceutical and Biomedical Analysis·Mario Thevis, Wilhelm Schänzer
Jun 1, 1983·The Proceedings of the Nutrition Society·P J Buttery
Sep 1, 1981·The Proceedings of the Nutrition Society·J G Schofield
Nov 10, 2009·Frontiers in Neuroendocrinology·T R CastañedaM H Tschöp
Mar 31, 2009·Surgical Oncology·Dimitrios NikolopoulosGregory Kouraklis
May 8, 2007·Biochemical and Biophysical Research Communications·Belisario DominguezEduardo Monjaraz
Jun 5, 2015·Molecular Metabolism·T D MüllerM H Tschöp
Sep 30, 2009·Journal of Peptide Science : an Official Publication of the European Peptide Society·Constance CholletAnnette G Beck-Sickinger
Dec 29, 2004·Regulatory Peptides·Hiroaki UenoMasamitsu Nakazato
Jul 21, 2004·Best Practice & Research. Clinical Endocrinology & Metabolism·Roy G SmithMark Asnicar
Jun 2, 2005·Domestic Animal Endocrinology·L L AndersonA Glavaski-Joksimovic
Oct 18, 2000·Growth Hormone & IGF Research : Official Journal of the Growth Hormone Research Society and the International IGF Research Society·M ZdravkovicM M Ilondo
Apr 14, 2006·Journal of Pharmacological Sciences·Hiroshi HosodaKenji Kangawa

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