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

doi:10.1021/jm00207a029

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

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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 language	English (US)
Pages (from-to)	993-995
Number of pages	3
Journal	Journal of Medicinal Chemistry
Volume	21
Issue number	9
DOIs	https://doi.org/10.1021/jm00207a029
State	Published - Jan 1 1978
Externally published	Yes

ASJC Scopus subject areas

Molecular Medicine
Drug Discovery

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title = "Cyclic Analogues of Luteinizing Hormone-Releasing Hormone with Significant Biological Activities",

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.",

author = "Janos Seprodi and Coy, {David H.} and Vilchez-Martinez, {Jesus A.} and Escipion Pedroza and Huang, {W. Y.} and Schally, {Andrew V.}",

year = "1978",

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doi = "10.1021/jm00207a029",

language = "English (US)",

volume = "21",

pages = "993--995",

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T1 - Cyclic Analogues of Luteinizing Hormone-Releasing Hormone with Significant Biological Activities

AU - Seprodi, Janos

AU - Coy, David H.

AU - Vilchez-Martinez, Jesus A.

AU - Pedroza, Escipion

AU - Huang, W. Y.

AU - Schally, Andrew V.

PY - 1978/1/1

Y1 - 1978/1/1

N2 - 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.

AB - 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.

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JF - Journal of Medicinal Chemistry

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IS - 9

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

Abstract

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