Preparation And Antiherpetic Activities Of Oligosaccharides From Kappa Carrageenan And Its Derivatives

Herpes simplex virus (HSV) is a class of highly infectious latent disease. At present, most of the anti-HSV drugs on the market have shortages, such as high toxicity, drug resistance, and so on. Therefore, it is an important and permanent task to develop high-effect and low-toxicity drugs for HSV treatment. Sulfated polysaccharides show a broad-spectrum antiviral activity, including HSV.In this paper,κ-carrageenan oligosaccharides are prepared by enzymatic hydrolysis. Sulfated derivatives and desulfated derivatives ofκ-carrageenan oligosaccharides are obtained respectively by using different sulfonation or desulfonation methods. Herpes simplex virus HSV-1 is used to study the antiherpesviral activities of oligosaccharides fromκ-carrageenan and its derivatives. The anticoagulation activities of oligosaccharides fromκ-carrageenan and its derivatives have also been studied on. The main results are listed below:Different ethanol-precipitated fractions of oligosaccharides fromκ-carrageenan have been obtained after enzymatic hydrolysis. By IR and chemical analysis, it can be concluded that enzymatic hydrolysis cannot destroy the chemical structure ofκ-carrageenan.Study on the best preparation conditions of sulfated and desulfated derivatives ofκ-carrageenan oligosaccharides is carried on by changing reagent combination, reaction temperature, and reaction time. In order to get its best sulfated and desulfated derivatives,κ-carrageenan oligosaccharides should be prepared with formamide- chlorosulfonic acid at 70℃for 6h, or DMSO-pyridine-1,2,4,5-prenitic-sodium fluoride at 100℃for 4h respectively.The antiherpetic mechanism ofκ-carrageenan oligosaccharides and its derivatives is studied by way of directly inactivating virus, inhabiting virus absorption, and influencing virus replication and release. The results show thatκ-carrageenan oligosaccharides and its sulfated derivatives have little cytotoxic effect on Vero cells, and could not directly inactivate HSV-1 or influence its replication and release, but inhabited HSV-1 absorption on the surface of cells. The sulfated derivatives ofκ-carrageenan oligosaccharides had stronger effects on HSV-1 absorption thanκ-carrageenan oligosaccharides with the same concentration. The desulfated derivatives ofκ-carrageenan oligosaccharides had no effect on HSV-1. So it could be concluded that there was a positive relationship between the content of sulfate radical ofκ-carrageenan oligosaccharides and its antiherpetic activity, which was achieved mainly via inhabiting HSV-1 absorption on the host cells.By testing t APTT and t PT ofκ-carrageenan oligosaccharides and its derivatives, it shows thatκ-carrageenan oligosaccharides and its derivatives have little effect on extrinsic coagulation system, but have effects on intrinsic coagulation system. Furthermore, the effects are related positively to the content of sulfate radical.