title: Immunostimulating activities of the novel peptidomimetic L-glutamyl-histamine.
abstract: An original representative of histamine-containing peptidomimetics L-glutamyl-histamine (L-Glu-Hist) was synthesized and characterized as a cytokine mimic leading to cellular responses of improved specificity. The energy-minimized 3-D conformations of L-Glu-Hist derived from its chemical structure resulted in stabilization for Fe(2+) chelating complexes. L-Glu-Hist accelerated the decrease of ferrous iron in the ferrous sulphate 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 Fe(2+) to phenanthroline due to binding of ferrous ions in chelating complexes. L-Glu-Hist showed a stimulatory effect on phosphatidylcholine liposomal peroxidation (LPO) catalysed by the superoxide anion radical (O(2) (*))-generating system (Fe(2+)+ 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 ( approximately 10 mm) L-Glu-Hist concentration. L-Glu-Hist released O(2) (*) in concentrations which stimulated [(3)H]-thymidine incorporation into DNA and proliferation of mouse spleen lymphocytes and mononuclear cells from human blood. The structural peptide-like analogues of L-Glu-Hist such as L-Glu-Trp, carcinine (beta-alanylhistamine), but not L-Pro-Glu-Trp were active in stimulating thymidine incorporation and in inducing proliferation of mononuclear cells compared to mitogen concanavalin A at doses 2.5-25.0 microg/ml. Our data provide evidence that L-Glu-Hist may act as a very fast and sensitive trigger for lymphocyte proliferation and immunoregulation.
authors.affiliation: Innovative Vision Products, Inc., Delaware, USA. markbabizhayev2004@yahoo.com
authors.forename: M A
authors.initials: MA
authors.lastname: Babizhayev
authors.forename: Y A
authors.initials: YA
authors.lastname: Semiletov
authors.forename: Y A
authors.initials: YA
authors.lastname: Lul'kin
authors.forename: N L
authors.initials: NL
authors.lastname: Sakina
authors.forename: E L
authors.initials: EL
authors.lastname: Savel'yeva
authors.forename: L M
authors.initials: LM
authors.lastname: Alimbarova
authors.forename: I P
authors.initials: IP
authors.lastname: Barinskii
mesh_terms: D000818:Animals; D018929:Cell Culture Techniques; D049109:Cell Proliferation / Q000187:drug effects; D003208:Concanavalin A / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005609:Free Radicals / Q000378:metabolism; D006801:Humans; D007502:Iron Chelating Agents / Q000494:pharmacology; D007963:Leukocytes, Mononuclear / Q000187:drug effects; D008213:Lymphocyte Activation / Q000187:drug effects; D008214:Lymphocytes / Q000187:drug effects*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008934:Mitogens / Q000494:pharmacology; D009842:Oligopeptides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D010084:Oxidation-Reduction; D011487:Protein Conformation
chemical_list: D005609:Free Radicals; D007502:Iron Chelating Agents; D008934:Mitogens; D009842:Oligopeptides; C120432:glutamyl-histamine; D003208:Concanavalin A
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