Cyclic Analogues of Luteinizing Hormone-Releasing Hormone with Significant Biological Activities

Janos Seprodi, David H. Coy, Jesus A. Vilchez-Martinez, Escipion Pedroza, W. Y. Huang, Andrew V. Schally

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

There is evidence that, in its receptor-binding conformation, the N and C terminus of LH-RH may be in close proximity and two cyclic analogues of the hormone were synthesized to test the hypothesis. Cyclic [β-Ala1,D-Ala6,Gly10]- and [6-aminohexanoic acid1,D-Ala6,Gly10]-LH-RH were prepared by treatment of their linear precursor peptides with dicyclohexylcarbodiimide in the presence of 1-hydroxybenzotriazole in dilute dimethylformamide solution. Although the linear peptides possessed no detectable LH-releasing activity in ovariectomized rats, the cyclic β-Ala analogue had 1.2% the activity of LH-RH, whereas the longer chain cyclic 6-aminohexanoic acid analogue had 0.65% activity. These results support the concept of an important interaction between the ends of the LH-RH molecule possibly involving hydrogen-bond formation between the pyrrolidone carbonyl group of pyroglutamic acid and the glycinamide group.

Original languageEnglish (US)
Pages (from-to)993-995
Number of pages3
JournalJournal of Medicinal Chemistry
Volume21
Issue number9
DOIs
StatePublished - Jan 1 1978
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

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