Alloferon-1

Alloferon-1 have been proposed as an effective peptide to enhance antitumoral immunity, antiviral defense and anti-inflammatory activity. This work aimed to assess anti-inflammatory effects of alloferon-1 against acute inflammation and histopathological deformations in λ-carrageenan-induced paw edema in mice. Systemic pretreatment with alloferon-1 (22.0 mg/kg) intraperitoneally injected mice showed a significant reduction in paw thickness and vascular permeability. Alloferon-1 prevented λ-carrageenan-evoked exudation and the neutrophil influx to the mouse pleura and the neutrophil migration into carrageenan-stimulated mouse air pouches based on the histopathological changes in the paw tissues. Administration of alloferon-1 also suppressed the expression of the inflammatory cytokines in the inflamed paw tissues such as tumor necrosis factor-α (TNF-α), monocyte chemoattractant protein 1 (MCP1), interleukin-5 (IL-5), etc. detected by Luminex liquid chip. Collectively, the present study provides evidences for the marked anti-inflammatory effects of alloferon-1 which might represent new therapeutic options for the treatment of acute inflammatory diseases.

Copper(II) complex formation processes between the alloferon 1 (Allo1) (HGVSGHGQHGVHG) analogues where the tryptophan residue is introducing in the place His residue H1W, H6W, H9W and H12W have been studied by potentiometric, UV-visible, CD and EPR spectroscopic, and MS methods. For all analogues of alloferon 1 complex speciation have been obtained for a 1:1 metal-to-ligand molar ratio and 2:1 of H1W because of precipitation at higher (2:1, 3:1 and 4:1) ratios. At physiological pH7.4 and a 1:1 metal-to-ligand molar ratio the tryptophan analogues of alloferon 1 form the CuH-1L and/or CuH-2L complexes with the 4N binding mode. The introduction of tryptophan in place of histidine residues changes the distribution diagram of the complexes formed with the change of pH and their stability constants compared to the respective substituted alanine analogues of alloferon 1. The CuH-1L, CuH-2L and CuH-3L complexes of the tryptophan analogues are more stable from 1 to 5 log units in comparison to those of the alanine analogues. This stabilization of the complexes may result from cation(Cu(II))-π and indole/imidazole ring interactions. The induction of apoptosis in vivo, in Tenebrio molitor cells by the ligands and their copper(II) complexes at pH7.4 was studied. The biological results show that copper(II) ions in vivo did not cause any apparent apoptotic features. The most active were the H12W peptide and Cu(II)-H12W complex formed at pH7.4.

Alloferon 1 is an insect-derived peptide with potent antimicrobial and antitumor activity. It was isolated from blood of an experimentally infected insect, the blow fly Callifora vicina. Synthetic alloferon 1 reveals a capacity to stimulate activity of NK cells and synthesis IFN in animal and human models. Moreover, it was demonstrated antiviral and antitumor activity of alloferon 1 in mice. There are no data on influence of alloferon 1 on central nervous system. The aim of present study was to determine an effect of alloferon 1 on rats' central nervous system by some behavioral tests: open field test, hole test, score of rats irritability, and determination of memory consolidation in the water maze test. Moreover, a probable antinociceptive effect of alloferon 1 in rats was determined by a tail immersion test and hot plate test. Experiments were performed on female Wistar rats. Seven days before experiments, rats were anesthetized with ketamine and xylazine and polyethylene cannulas were implanted into the right lateral brain ventricle (i.c.v.). On the day of experiment, alloferon 1 dissolved in a volume of 5 μL of saline was injected directly i.c.v. through implanted cannulas at doses of 5-100 nmol. It was found that alloferon 1 had slight effect on locomotor and exploratory activity, induced some decrease of rat irritability and a weak impairment of rats memory (only at the low dose of 5 nmol). On the other hand, the higher dose of this peptide exerts significant antinociceptive effect. Obtained results indicate that alloferon 1 do not exert any evidently toxic effect on central nervous system in rats. Therefore, alloferon 1 may be good new drug with antitumor and antinociceptive activity.