Relative Potencies of Antagonists of the Luteinizing Hormone Releasing Hormone with Lys8 and Arg8 and Substitutions in Positions 3 ,5 ,6 ,7 and 8

Author:

Folkers Karl1,Bowers Cyril2,Tang Pui-Fun L.1,Kobota Minoru1,Shao-bo Xiao1,Bender Wolfgang1,Yin-Zeng Liu1

Affiliation:

1. 1The Institute for Biomedical Research, The University of Texas at Austin, Austin, Texas 78712

2. 2Director of Endocrine Unit, Tulane University School of Medicine, 1430 Tulane Avenue, New Orleans, Louisiana 70112

Abstract

Abstract Antagonists of the luteinizing hormone releasing hormone (LHRH) of increased potency is a goal for control of ovulation. In the design and synthesis of 26 decapeptides, emphasis was given to analogs with Lys8 and Arg8 and with various substitutions in positions 3, 5, 6, 7 and 8. Two antagonists, [N-Ac-ᴅ-2-Nal1,ᴅ-pClPhe2,ᴅ-3-Pal3,Ser4,Tyr5,ᴅ-Arg6,Leu7,Lys8,Pro9,ᴅ-Ala10] - NH2 and [N-Ac-ᴅ-2-Nal1.ᴅ-pClPhe2,ᴅ-3-Pal3,Ser4,Arg5,ᴅ-3-Pal6,Leu7,Arg8,Pro9,ᴅ-Ala10]-NH2 showed 80-85% antiovulatory activity (AOA) at 0.25 μg in the rat. The latter antagonist showed 60% AOA at 0.125 μg. Of four pairs of analogs with Arg8 and Lys8, respectively, two pairs favored Lys8 over Arg8 for potency. One pair showed negligible difference and another pair favored Arg8 over Lys8. There is specificity of substitution for potency. In other antagonists, ᴅ-3- Pal3, Tyr5 or Phe5, ᴅ-Arg6 and Leu7 or Nle7 or Val7 and Arg8 were variously effective substitutions for increase of potency and reduction of histamine release.

Publisher

Walter de Gruyter GmbH

Subject

General Biochemistry, Genetics and Molecular Biology

Cited by 6 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

1. On the bosonic symmetries of the Dirac equation with nonzero mass;Journal of Physics: Conference Series;2019-04

2. Antagonists of luteinizing hormone releasing hormone with novel unnatural amino acids at position six;International Journal of Peptide and Protein Research;2009-01-12

3. Bosonic symmetries of the massless Dirac equation;Advances in Applied Clifford Algebras;1998-06

4. Solutions of the Maxwell equations describing the spectrum of hydrogen;Ukrainian Mathematical Journal;1997-07

5. Luteinising Hormone Releasing Hormone;Small Peptides - Chemistry, Biology and Clinical Studies;1993

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