Branched-Chain Analogues of Luteinizing Hormone-Releasing Hormone

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

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

Benzoyl-, acetylsalicylyl-, indomethacinyl-, pyroglutamylhistidyl-, and pyroglutamyl-D-phenylalanyl-D-tryptophanylseryltyrosyl groups were attached to a moderately active inhibitory analogue of LH-RH, [D-Phe2,D-Trp3,-D-Lys6]-LH-RH, via the ε-amino group of the lysine residue. The resulting compounds were assayed for anti-LH-RH activity and for their ability to block ovulation in the rat. The decrease in polarity and increase in size of the lysine side chain resulting from addition of the aromatic acyl groups gave almost no increase in inhibitory activity. Addition of the dipeptide, <Glu-His, also had little effect on potency. However, incorporation of the pentapeptide sequence to give a branched pentadecapeptide with essentially two N termini resulted in antiovulatory activity greater than the parent peptide or any other analogue thus far tested by us. The corresponding agonist peptide, [Nε-(<Glu-His-Trp-Ser-Tyr)-D-Lys6]-LH-RH, was also synthesized and tested for LH- and FSH-releasing activity. Surprisingly, it was no more active than [D-Lys6]-LH-RH itself, suggesting that an intact C terminus as well as an N terminus is necessary for the full expression of gonadotropin release.

Original languageEnglish (US)
Pages (from-to)276-280
Number of pages5
JournalJournal of Medicinal Chemistry
Volume21
Issue number3
DOIs
StatePublished - Jan 1 1978

    Fingerprint

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

Cite this