Non-mammalian GnRH analogs and uses thereof in tumor cell...

Details Non-mammalian GnRH analogs and uses thereof in tumor cell... Non-mammalian GnRH analogs and uses thereof in tumor cell...

2000-03-31

2010-11-16

Allen, Marianne P (Department: 1647)

Chemistry: natural resins or derivatives; peptides or proteins;

Peptides of 3 to 100 amino acid residues

Lutenizing hormone releasing factor ; related peptides

C530S328000, C530S332000, C530S333000, C530S335000, C514S002600, C514S015800

Reexamination Certificate

active

07834141

ABSTRACT:
Specially designed non-mammalian GnRH analogs resistant to degradation by the tumor tissue enzymes, post-proline peptidases as well as endopeptidases, are disclosed. The GnRH analogs are further defined as analogs of chicken II GnRH, salmon GnRH, or herring GnRH, but can include any non-mammalian GnRH analog with similar amino acid structure. These non-mammalian analogs incorporate D-arginine, D-leucine, D-tBu-Serine or D-Trp or other similar amino acids at position 6 and ethylamide or aza-Gly-amide or similar amides at position 10. These analogs demonstrate preferential binding to tumor cell GnRH receptors that is greater relative to the binding of the mammalian analogs to the tumor cell GnRH receptor. These non-mammalian GnRH analogs may be used in pharmaceutical preparations, and it specifically in various treatments as an anti-tumor, anti-proliferation, anti-metastatic and/or an apoptotic agent. The non-mammalian GnRH analogs are also provided in pharmaceutical preparations that may be used clinically for tumor regression when used in very low doses and administered in pulsatile fashion.

REFERENCES:
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patent: 6635739 (2003-10-01), Siler-Khodr
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White et al. A second gene for gonadotropin-releasing hormone:cDNA and expresssion pattern in the brain. Proc. Natl. Acad. Sci. USA vol. 91 1423-1427 (1994).
Lovejoy et al. Structural modifications of non-mammalian gonadotropin-releasing hormone (GnRH) isoforms: design of novel GnRH analogues. Regulatory Peptides vol. 60:99-115 (1995).

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