Glyco-proteins derived from Halobacterium salinarium - useful in treatment and prophylaxis of diseases by non-specifically stimulating the immune system

Glycoproteins including the aminoacid sequence Glu-Glu-Pro-Asp-Gln-Thr-Thr-Val-Asp- Gln-Pro-Glu-Asn-Asn'-Gln-Thr-Met-Thr' -Thr'-Thr'-Met-Thr-Glu in which Asp' and Thr' respectively are bound to an acidic oligosaccharide by an N-glycosidic bonding and by a complete or partial O-glycosidic bonding to a neutral oligosaccharide are new. The glycopeptides may be elongated at (i) their N-terminus by up to 740 aminoacids (AA), and at their (ii) C-terminus by up to 54 AA, possible including N- and O-glycosidically bound oligosaccharides and/or polysaccharides. USE/ADVANTAGE - The glycopeptides are useful in medicaments for therapy and prophylaxis of patients with bacterial, viral, fungal and parasitic infections by boosting the unspecific body defence. The new glycopeptides are more effective in protection against infection and in increasing the colony stimulating factor (CSF). In an example, the 600 bp fragment of H.salinarious DSM668 was cleaved with subtilisin and the glycoproteins of the sequence above were shown to have a very good immunostimulating activity. The activation of tumour necrosis factor (TNF) activity in sera was determined by cytolysis of TNF-sensitive WEHI164/13 cells. NMRI mice together with WEHI-cells in FCS/RPMI medium were incubated overnight at 37 deg.C and 7% CO2. The TNF serum level was increased after treatment with the glycoprotein. To test the prophylaxis for acute infections (peritonitis, sepsis) 24 mice were either treated with the glycoprotein or glycopeptide or with physiological NaCl soln.. After 24 hr they were injected intraperitoneally with 10x LD50 of Staphylococcus aureus ATCC13709. After 7 days, none, 3/24 and 9/24 mice treated with 10 mg/kg of NaCl glycoprotein and glycopeptide respectively survived. 0/24, 6/24 and 12/24 survived when treated with NaCl, glycoprotein and glycopeptides respectively.