Plain Language Summary
Scientists created highly potent and enzyme-resistant analogs of growth hormone-releasing hormone by strategically replacing certain amino acids that are normally vulnerable to the digestive enzyme trypsin. The best analogs were completely resistant to trypsin digestion and roughly 50 times more potent than standard GHRH when injected under the skin in rats. These stabilized peptides are promising candidates for clinical use in treating growth hormone deficiency.
Abstract
A series of analogues of hGH-RH-(1-29)-NH2 designed to have metabolic stability has been synthesized. Standard Boc-SPPS was employed, modified to permit the guanidinylation of amino side-chains after chain assembly but before release from the resin. [Dat1, Har(11, 12, 20, 21, 29), Ala15, Nle27, Asp28]-, [Dat1, Har(11, 20, 29), Orn12, Ala15, Nle27, Asp28]-, and [Dat1, Gap(11,12, 21, 29), Ala15, Har20, Nle27, Asp28]-hGH-RH-(1-29)-NH2 were completely resistant to trypsin and about 50 times as potent as hGH-RH-(1-29)-NH2 itself when injected subcutaneously in rats. These peptides are candidates for clinical application in the therapy of GH deficiency.
Authors
Izdebski, Jan; Witkowska, Ewa; Kunce, Danuta; Orłowska, Alicja; Baranowska, Bogusława; Wolińska-Witort, Ewa