Potent Trypsin‐resistant hGH‐RH Analogues

A series of analogues of hGH‐RH‐(1–29)‐NH 2 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. [Dat 1 , Har 11, 12, 20, 21, 29 , Ala 15 , Nle 27 , Asp 28 ]‐, [Dat 1 , Har 11, 20, 29 , Orn 12 , Ala 15 , Nle 27 , Asp 28 ]‐, and [Dat 1 , Gap 11, 12, 21, 29 , Ala 15 , Har 20 , Nle 27 , Asp 28 ]‐hGH‐RH‐(1–29)‐NH 2 were completely resistant to trypsin and about 50 times as potent as hGH‐RH‐(1–29)‐NH 2 itself when injected subcutaneously in rats. These peptides are candidates for clinical application in the therapy of GH deficiency. Copyright © 2004 European Peptide Society and John Wiley & Sons, Ltd.