Synthesis and Biological Activity of LH-RH Analogs Modified at the Carboxyl Terminus

David H. Coy, Esther J. Coy, Andrew V. Schally, Jesus A. Vilchez-Martinez

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

Des(Pro9,Gly10)-LH-RH ethylamide, des(Pro9,Gly10)-LH-RH butylamide, desGly10-LH-RH 2-aminoethylamide, and desGly10-LH-RH hydrazide were synthesized by a solid-phase method involving cleavage of protected peptide intermediates from their resin support by reaction with ethylamine, butylamine, ethylenediamine, and hydrazine, respectively. In the assay utilizing steroid pretreated, ovariectomized rats, the peptides were found to have the following LH-releasing activities when compared with natural LH-RH: ethylamide, 0.2%; butylamide, 0.1%; 2-aminoethylamide, 2.4%; hydrazide, 12%. DesGly10-LH-RH hydrazide was used as a precursor in the synthesis of desGly10-LH-RH allylamide and desGly10-LH-RH propargylamide by conversion to the azide and reaction with allylamine and propargylamine, respectively. LH and FSH levels were measured over a 4-hr period after subcutaneous injection of these two peptides into immature male rats in order to detect any prolongation of activity. The allylamide analog was quite active, releasing 1.7 times more LH and 1.3 times more FSH than the same dose of LH-RH. The propargylamide analog was considerably less active, exhibiting 50% LH-releasing activity and 64% FSH-releasing activity. Neither peptic e appeared to be longer acting than LH-RH.

Original languageEnglish (US)
Pages (from-to)275-277
Number of pages3
JournalJournal of Medicinal Chemistry
Volume18
Issue number3
DOIs
StatePublished - Mar 1 1975
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

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