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Maria Keramida John M. Matsoukas Dimitris Panagiotopoulos Kostas Alexopoulos Elizabeth Matsoukas John Cladas Vasilis A. Tzingounis Emmanuel Cardamakis Hernâni L. S. Maia Debanaba Pati Hamid R. Habibi 《Letters in Peptide Science》1996,3(4):257-262
Summary Gonadotropin-releasing hormone (GnRH) stimulates the release and synthesis of gonadotropin hormones (GtH) and is the key regulator of reproduction. The present study was carried out to design a potent GnRH analogue containing Tyr(OMe) at position 5 and ad-amino acid at position 6. This was based on a previous study in which [Tyr(OMe)5]GnRH was shown to have reduced potency compared to GnRH. A novel GnRH peptide containing Tyr(OMe)5 andd-Glu6 in combination with other substitutions at positions 9 and 10 was synthesized in the present study and tested for binding to the rat pituitary as well as potency in terms of gonadotropin (GtH) release in the goldfish pituitary and ovulation in sea bass. The results demonstrate that the replacement of the glycine residue at position 6 with ad-Glu in combination with the substitution of proline at position 9 with azetidine (Aze) increased the binding and biological activity of [Tyr(OMe)5]GnRH. The observed increased potency is likely to be related to the improved resistance to degradation. The present findings may lead to the development of a more potent GnRH agonist for inducing ovulation in fish. 相似文献
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Keramida Maria Matsoukas John M. Agelis George Panagiotopoulos Dimitris Cladas John Pati Debanada Moore Graham J. Habibi Hamid R. 《International journal of peptide research and therapeutics》1998,5(4):305-315
Summary We have recently reported the synthesis and the conformational properties of some Gonadotropin-releasing hormone (GnRH) analogues
in which the tyrosine residue at position 5 is substituted with tyrosine-O-methyl (Keramida et al., Let. Pept. Sci., 3 (1996)
257/Matsoukas et al., Eur. J. Med. Chem., 32 (1997) 927). The analogue [Tyr-(OMe)5]-GnRH was found to exert a lower degree of desensitization than the native GnRH peptides in terms of pituitary gonadotropin
(GTH) release in goldfish. Compared to GnRH, however, [Tyr-(OMe)5]-GnRH exerted a lower GTH-release potency in cultured goldfish pituitary fragments, and was bound with a lower binding affinity
to the rat pituitary GnRH receptors. In order to increase the potency of [Tyr-(OMe)5]-GnRH, we have synthesized a group of GnRH peptides containing Tyr-(OMe)5 in combination with other substitutions at positions 6, 9 and 10 and we have estimated their binding affinity for the rat
pituitary receptors and gonadotropin (GTH) release potency in the goldfish pituitary. A selected number of these analogues
was also tested for their ability to induce ovulation in seabass. The important structural modifications that increased the
binding and gonadotropic activity of [Tyr(OMe)5]-GnRH in vitro and in vivo were found to include the replacement of the proline at position 9 with azetidine, glycine amide
terminus with an alkyl amide group and Gly6 residue with hydrophilicd-amino acids such asd-Arg6. Overall, the findings provide SAR information on a group of novel GnRH peptides that can be also used to induce ovulation
in teleosts. 相似文献
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Maria Keramida John M. Matsoukas George Agelis Dimitris Panagiotopoulos John Cladas Debanada Pati Graham J. Moore Hamid R. Habibi 《Letters in Peptide Science》1998,5(4):305-315
We have recently reported the synthesis and the conformational properties of some Gonadotropin-releasing hormone (GnRH) analogues in which the tyrosine residue at position 5 is substituted with tyrosine-O-methyl (Keramida et al., Let. Pept. Sci., 3 (1996) 257/Matsoukas et al., Eur. J. Med. Chem., 32 (1997) 927). The analogue [Tyr-(OMe)5]-GnRH was found to exert a lower degree of desensitization than the native GnRH peptides in terms of pituitary gonadotropin (GTH) release in goldfish. Compared to GnRH, however, [Tyr-(OMe)5]-GnRH exerted a lower GTH-release potency in cultured goldfish pituitary fragments, and was bound with a lower binding affinity to the rat pituitary GnRH receptors. In order to increase the potency of [Tyr-(OMe)5]-GnRH, we have synthesized a group of GnRH peptides containing Tyr-(OMe)5 in combination with other substitutions at positions 6, 9 and 10 and we have estimated their binding affinity for the rat pituitary receptors and gonadotropin (GTH) release potency in the goldfish pituitary. A selected number of these analogues was also tested for their ability to induce ovulation in seabass. The important structural modifications that increased the binding and gonadotropic activity of [Tyr(OMe)5]-GnRH in vitro and in vivo were found to include the replacement of the proline at position 9 with azetidine, glycine amide terminus with an alkyl amide group and Gly6 residue with hydrophilic D-amino acids such as D-Arg6. Overall, the findings provide SAR information on a group of novel GnRH peptides that can be also used to induce ovulation in teleosts. 相似文献
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