The fragmentation and transformation of beta-oxidized N-nitrosamines in relation to their analysis and occurrence.
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Biomedical subjects
Publications and source records attributed to W A McKinley.
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Various analogs of synthetic hypothalamic luteinizing hormone-releasing hormone (LH-RH) were evaluated for agonistic (ovulation-inducing), postcoital contraceptive, and direct uterotrophic activities. All analogs showing agonistic activity also possessed the ability to terminate pregnancy, as did LH-RH; there appeared to be a direct relationship between agonistic and postcoital potency and activity. The highly potent and active LH-RH agonist, D-[Ala]6-des-[Gly]10-pro9-ethylamide-LH-RH, proved to be the most potent and active postcoital preimplantational and postimplantational antifertility agent. In contrast to LH-RH, none of the analogs tested in the hypophysectomized animal produced a uterotrophic effect, revealing a selective extrapituitary effect of the parent hormone. The collective data demonstrate that peptides derived from LH-RH and bearing agonistic properties can terminate pregnancy postcoitally, via disruption of the pituitary-ovarian reproductive complex. Possible mechanisms are discussed, and the use of members of this neurohormonal class as potential profertility agents should be weighed with caution.
Seven synthetic analogues of somatostatin helped clarify structural requirements for suppression of growth hormone secretion in rats. Size of the ring is not critical; deletions of serine-13, lysine-4 or asparagine-5 result in peptides which retain an appreciable fraction of the activity. The analogue des-Ala1, Gly2, Asn5-somatostatin lowers plasma growth hormone and insulin levels without affecting plasma glucagon levels significantly.
Ten analogs of luteinizing hormone-releasing hormone (LH-RH) substituted in position 2 with D-amino acids and at 6 with either a D-amino acid or a nonasymmetric amino acid were synthesized by solid-phase methodology and assayed for antiovulatory activity. [D-Phe2]-LH-RH substituted in the 6 position with D-Ala, D-Leu, D-Arg, D-(Ph)Gly, D-Phe, or 2-Me-Ala possessed varying degrees of antiovulatory activity. [D-p-F-Phe2-D-Ala6]-LH-RH was one of the most active antiovulatory compounds, while the [D-p-Cl-Phe2-D-Ala6]-LH-RH analog was devoid of activity at a comparable dose.
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