Synthesis and biological activity of LH-RH antagonists modified in position 1

Aniko Horvath; David H. Coy; Mary V. Nekola; Esther J. Coy; Andrew V. Schally; Istvan Teplan

doi:10.1016/0196-9781(82)90066-3

Synthesis and biological activity of LH-RH antagonists modified in position 1

Aniko Horvath, David H. Coy, Mary V. Nekola, Esther J. Coy, Andrew V. Schally, Istvan Teplan

Research output: Contribution to journal › Article › peer-review

28 Scopus citations

Abstract

As part of our studies on the design of more potent antagonists of the LH-RH (luteinizing hormone-releasing hormone) decapeptide, twelve new highly soluble D-Arg⁶-analogs have been synthesized. These peptides contain modifications in position 1 and are typified by the general formula (N-acetyl-X¹, D-p-Cl-Phe², D-Trp³, D-Arg⁶, D-Ala¹⁰) LH-RH. We have found that a lypophilic, aromatic substituent is required in position 1 in order to elicit antiovulatory activity at a dose as low as 3 μg. The larger the hydrophobic amino acid (X: p-Br-Phe, β-Nal-2) in position 1, the higher is the antiovulatory activity that can be attained. Analogs with non-aromatic or hydrophilic amino acids (X: Gly, Leu, Arg, His, Glu) in position 1 generally have much lower activities in this series of LH-RH antagonists.

Original language	English (US)
Pages (from-to)	969-971
Number of pages	3
Journal	Peptides
Volume	3
Issue number	6
DOIs	https://doi.org/10.1016/0196-9781(82)90066-3
State	Published - Jan 1 1982
Externally published	Yes

Keywords

Antiovulatory activity
LH-RH antagonists
Peptide synthesis

ASJC Scopus subject areas

Biochemistry
Endocrinology
Physiology
Cellular and Molecular Neuroscience

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title = "Synthesis and biological activity of LH-RH antagonists modified in position 1",

abstract = "As part of our studies on the design of more potent antagonists of the LH-RH (luteinizing hormone-releasing hormone) decapeptide, twelve new highly soluble D-Arg6-analogs have been synthesized. These peptides contain modifications in position 1 and are typified by the general formula (N-acetyl-X1, D-p-Cl-Phe2, D-Trp3, D-Arg6, D-Ala10) LH-RH. We have found that a lypophilic, aromatic substituent is required in position 1 in order to elicit antiovulatory activity at a dose as low as 3 μg. The larger the hydrophobic amino acid (X: p-Br-Phe, β-Nal-2) in position 1, the higher is the antiovulatory activity that can be attained. Analogs with non-aromatic or hydrophilic amino acids (X: Gly, Leu, Arg, His, Glu) in position 1 generally have much lower activities in this series of LH-RH antagonists.",

keywords = "Antiovulatory activity, LH-RH antagonists, Peptide synthesis",

author = "Aniko Horvath and Coy, {David H.} and Nekola, {Mary V.} and Coy, {Esther J.} and Schally, {Andrew V.} and Istvan Teplan",

year = "1982",

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AU - Horvath, Aniko

AU - Coy, David H.

AU - Nekola, Mary V.

AU - Coy, Esther J.

AU - Schally, Andrew V.

AU - Teplan, Istvan

PY - 1982/1/1

Y1 - 1982/1/1

N2 - As part of our studies on the design of more potent antagonists of the LH-RH (luteinizing hormone-releasing hormone) decapeptide, twelve new highly soluble D-Arg6-analogs have been synthesized. These peptides contain modifications in position 1 and are typified by the general formula (N-acetyl-X1, D-p-Cl-Phe2, D-Trp3, D-Arg6, D-Ala10) LH-RH. We have found that a lypophilic, aromatic substituent is required in position 1 in order to elicit antiovulatory activity at a dose as low as 3 μg. The larger the hydrophobic amino acid (X: p-Br-Phe, β-Nal-2) in position 1, the higher is the antiovulatory activity that can be attained. Analogs with non-aromatic or hydrophilic amino acids (X: Gly, Leu, Arg, His, Glu) in position 1 generally have much lower activities in this series of LH-RH antagonists.

AB - As part of our studies on the design of more potent antagonists of the LH-RH (luteinizing hormone-releasing hormone) decapeptide, twelve new highly soluble D-Arg6-analogs have been synthesized. These peptides contain modifications in position 1 and are typified by the general formula (N-acetyl-X1, D-p-Cl-Phe2, D-Trp3, D-Arg6, D-Ala10) LH-RH. We have found that a lypophilic, aromatic substituent is required in position 1 in order to elicit antiovulatory activity at a dose as low as 3 μg. The larger the hydrophobic amino acid (X: p-Br-Phe, β-Nal-2) in position 1, the higher is the antiovulatory activity that can be attained. Analogs with non-aromatic or hydrophilic amino acids (X: Gly, Leu, Arg, His, Glu) in position 1 generally have much lower activities in this series of LH-RH antagonists.

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