Potent trypsin-resistant hGH-RH analogues.
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.
Izdebski
Jan
J
Peptide Laboratory, Department of Chemistry, Warsaw University, Pasteura 1, 02-093 Warsaw, Poland. izdebski@chem.uw.edu.pl
Witkowska
Ewa
E
Kunce
Danuta
D
Orłowska
Alicja
A
Baranowska
Bogusława
B
Wolińska-Witort
Ewa
E
D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D001681:Biological Assay; D006801:Humans; D008969:Molecular Sequence Data; D051381:Rats; D017208:Rats, Wistar; D017337:Sermorelin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology*; D014357:Trypsin / Q000737:chemistry / Q000378:metabolism*
D017337:Sermorelin; D014357:Trypsin