Hydrostatin-TL1, an Anti-Inflammatory Active Peptide from the Venom Gland of Hydrophis cyanocinctus in the South China Sea.

Tumor necrosis factor (TNF)-α is a pleiotropic cytokine with intense pro-inflammatory and immunomodulatory properties, and anti-TNF-α biologics are effective therapies for various inflammatory diseases such as inflammatory bowel disease (IBD) and sepsis. Snake venom, as a traditional Chinese medicine, has been used in the treatment of inflammatory diseases in China for centuries. In this research, we constructed a venom gland T7 phage display library of the sea snake Hydrophis cyanocinctus to screen bioactive compounds that antagonize TNF-α and identified a novel nine-amino-acid peptide, termed hydrostatin-TL1 (H-TL1). In enzyme-linked immunosorbent assay (ELISA) and surface plasmon resonance (SPR) analyses, H-TL1 inhibited the interaction between TNF-α and TNF receptor 1 (TNFR1). Further, H-TL1 attenuated the cytotoxicity of TNF-α in L929 cells as determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. H-TL1 also decreased the mRNA expression of TNF-α/TNFR1 downstream targets and suppressed the phosphorylation of well-characterized proteins of downstream signal transduction pathways in HEK-293 cells. In vivo data demonstrated that H-TL1 protects animals against dextran sodium sulfate (DSS)-induced acute colitis and lipopolysaccharide (LPS)-induced acute shock. Given its significant anti-inflammatory activity in vitro and in vivo, H-TL1 is a potential peptide for the development of new agents to treat TNF-α-associated inflammatory diseases.

Synthesis of (2'S)- and (2'R)-2'-deoxy-2'-[(2-methoxyethoxy)amino] pyrimidine nucleosides and oligonucleotides.

Syntheses of specified 2'-modified nucleosides were achieved: a) via oximation of the 5',3'-blocked 2'-oxocytidine, followed by reduction, or b) by intramolecular nucleophilic addition of 3'-(2-methoxyethoxy)carbamate to the 2'-position with opening of O(2),2'-anhydrouridine. For the first time, 3'-phosphoroamidites of these 2'-modified nucleosides were successfully incorporated into oligonucleotides by solid-phase synthesis. Incorporation of 2'-modified nucleotides into oligodeoxyribonucleotides had a negative effect on the duplex T(m) values with the DNA or RNA complements. Nevertheless, modified nucleotides have shown good target recognition; the (S)-isomer binds preferably to RNA and the (R)-isomer to DNA. Both modified nucleosides significantly increased nuclease resistance of the oligodeoxyribonucleotides.

Effects of three fractions obtained from Naja haje venom on hemolysis and lipid metabolism in rabbits

Three fractions (F1, F2 and F3) were obtained from the venom of the Egyptian cobra Naja haje by gel filtration. F1 and F2 had indirect hemolytic effects on rabbit erytrocytes. The HU50 (the amount of the fraction causing 50 per cent hemolysis) values of F1 and F2 were 12.04 ñ 3.89 and 36.57 ñ 2.20 ug, respectively. The effects of the three cobra venom fractions on lipid metabolism were studied after 1, 2 3 and 4 hours. Serum total lipids and cholesterol were significantly decreased at almost all tested times, but variable changes were observed in the serum triglycerides. Serum inorganic phosphorus levels were significantly increased with F1 and F2 administration more than that with the F3 fraction. These results suggest that F1 and F2 possess phospholipase A2-like activities and their effects on the lipid metabolism is more intense than that of F3.