کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10836280 | 1066417 | 2005 | 13 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
3D molecular modeling, free radical modulating and immune cells signaling activities of the novel peptidomimetic l-glutamyl-histamine: possible immunostimulating role
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: 3D molecular modeling, free radical modulating and immune cells signaling activities of the novel peptidomimetic l-glutamyl-histamine: possible immunostimulating role 3D molecular modeling, free radical modulating and immune cells signaling activities of the novel peptidomimetic l-glutamyl-histamine: possible immunostimulating role](/preview/png/10836280.png)
چکیده انگلیسی
An original representative of the patented by author family of histamine-containing peptidomimetics l-glutamyl-histamine (l-Glu-Hist) was synthesized and characterized as a biologically active compound with a role of cytokine mimic leading to cellular responses of improved specificity. The study assesses the ability of l-Glu-Hist to affect molecular modeling, modulate free radical activity and influence immune cell signaling. The energy-minimized 3D conformations of l-Glu-Hist derived from its chemical structure resulted in stabilization for Fe2+ chelating complexes. l-Glu-Hist accelerated the decrease of ferrous iron in the ferrous sulfate solution in a concentration-dependent mode and showed the ferroxidase-like activity at concentrations less than 3 mM in the phenanthroline assay, whereas in the concentration range 3-20 mM l-Glu-Hist restricted the availability of Fe2+ to phenanthroline due to binding of ferrous ions in chelating complexes. l-Glu-Hist showed stimulatory effect on phosphatidylcholine liposomal peroxidation (LPO) catalyzed by the superoxide anion radical (O2â)-generating system (Fe2+ + ascorbate) at low (less or about 1 mM) l-Glu-Hist concentrations and both revealed the inhibitory effect on LPO in this system of high (â¼10 mM) l-Glu-Hist concentration. The stimulation of LPO by l-Glu-Hist was related to the ability of peptidomimetic in small (â¼0.05 mM) concentrations to release O2â free radicals as determined by the superoxide dismutase-inhibitable cytochrome c reduction assay. O2â release by l-Glu-Hist might result from its ferroxidase-like activity, while inhibition of LPO by l-Glu-Hist was caused by its chelating activity to Fe2+ ions, prevention of free radical generation and lipid hydroperoxide-degrading ability of 5-20 mM l-Glu-Hist. l-Glu-Hist released O2â in concentrations which stimulated [3H]-thymidine incorporation into DNA and proliferation of mouse spleen lymphocytes and mononuclear cells from human blood. l-Glu-Hist modulates the ability of oxygen free radicals to act as signaling agents at low concentrations, influencing gene expression. The structural peptide-like analogues of l-Glu-Hist such as l-Glu-Trp, carcinine (β-alanylhistamine), but not l-Pro-Glu-Trp were active in stimulating thymidine incorporation and in inducing proliferation of mononuclear cells as compared to mitogen concanavalin A at doses 2.5-25.0 μg/ml. Our data provide evidence that l-Glu-Hist may act as a very fast, specific and sensitive trigger for lymphocyte proliferation and immunoregulation. The cited abilities and further obtained in vivo results make Immudilin® ((INCI: glutamylamidoethyl imidazole, aqueous solution), l-Glu-Hist) a useful immunoregulatory agent.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Peptides - Volume 26, Issue 4, April 2005, Pages 551-563
Journal: Peptides - Volume 26, Issue 4, April 2005, Pages 551-563
نویسندگان
Mark A. Babizhayev, Yuri A. Semiletov, Yuri A. Lul'kin, Natalia L. Sakina, Ekaterina L. Savel'yeva, Ludmila M. Alimbarova, Igor Ph. Barinskii,