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 Citations (Scopus)

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
Pages (from-to)276-280
Number of pages5
JournalJournal of Medicinal Chemistry
Volume21
Issue number3
StatePublished - Dec 1 1978
Externally publishedYes

Fingerprint

Gonadotropin-Releasing Hormone
Lysine
Peptides
Dipeptides
Ovulation
Gonadotropins
Rats

ASJC Scopus subject areas

  • Organic Chemistry

Cite this

Seprodi, J., Coy, D. H., Vilchez-Martinez, J. A., Pedroza, E., & Schally, A. V. (1978). Branched-chain analogues of luteinizing hormone-releasing hormone. Journal of Medicinal Chemistry, 21(3), 276-280.

Branched-chain analogues of luteinizing hormone-releasing hormone. / Seprodi, Janos; Coy, David H.; Vilchez-Martinez, Jesus A.; Pedroza, Escipion; Schally, Andrew V.

In: Journal of Medicinal Chemistry, Vol. 21, No. 3, 01.12.1978, p. 276-280.

Research output: Contribution to journalArticle

Seprodi, J, Coy, DH, Vilchez-Martinez, JA, Pedroza, E & Schally, AV 1978, 'Branched-chain analogues of luteinizing hormone-releasing hormone', Journal of Medicinal Chemistry, vol. 21, no. 3, pp. 276-280.
Seprodi J, Coy DH, Vilchez-Martinez JA, Pedroza E, Schally AV. Branched-chain analogues of luteinizing hormone-releasing hormone. Journal of Medicinal Chemistry. 1978 Dec 1;21(3):276-280.
Seprodi, Janos ; Coy, David H. ; Vilchez-Martinez, Jesus A. ; Pedroza, Escipion ; Schally, Andrew V. / Branched-chain analogues of luteinizing hormone-releasing hormone. In: Journal of Medicinal Chemistry. 1978 ; Vol. 21, No. 3. pp. 276-280.
@article{179e0b73454e4f09a411b46bb8d29e1d,
title = "Branched-chain analogues of luteinizing hormone-releasing hormone",
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.",
author = "Janos Seprodi and Coy, {David H.} and Vilchez-Martinez, {Jesus A.} and Escipion Pedroza and Schally, {Andrew V}",
year = "1978",
month = "12",
day = "1",
language = "English",
volume = "21",
pages = "276--280",
journal = "Journal of Medicinal Chemistry",
issn = "0022-2623",
publisher = "American Chemical Society",
number = "3",

}

TY - JOUR

T1 - Branched-chain analogues of luteinizing hormone-releasing hormone

AU - Seprodi, Janos

AU - Coy, David H.

AU - Vilchez-Martinez, Jesus A.

AU - Pedroza, Escipion

AU - Schally, Andrew V

PY - 1978/12/1

Y1 - 1978/12/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=0018178246&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0018178246&partnerID=8YFLogxK

M3 - Article

VL - 21

SP - 276

EP - 280

JO - Journal of Medicinal Chemistry

JF - Journal of Medicinal Chemistry

SN - 0022-2623

IS - 3

ER -