Immunostimulating activities of the novel peptidomimetic L-glutamyl-histamine.
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.
Babizhayev
M A
MA
Innovative Vision Products, Inc., Delaware, USA. markbabizhayev2004@yahoo.com
Semiletov
Y A
YA
Lul'kin
Y A
YA
Sakina
N L
NL
Savel'yeva
E L
EL
Alimbarova
L M
LM
Barinskii
I P
IP
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
D005609:Free Radicals; D007502:Iron Chelating Agents; D008934:Mitogens; D009842:Oligopeptides; C120432:glutamyl-histamine; D003208:Concanavalin A
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