Heparin-selenocystamine conjugate with selenol groups

Heparin-selenocystamine conjugate, which was intended to mimic the heparin-selenoprotein P complex, was prepared. The conjugate had glutathione peroxidase-like activity and activity was observed toward hydrogen peroxide, tert-butyl hydroperoxide, and cumene hydroperoxide. The ultraviolet spectrum of an aqueous solution of the conjugate was stable and had a similar shape to that observed transiently when selenocystamine was reduced by sodium cyanoborohydride; this suggests that the diselenide bond of selenocystamine introduced into heparin was cleaved during conjugate preparation and the selenol group is preserved. The conjugate reacted to the same degree as cysteine with 5,5'-dithiobis (2-nitrobenzoic acid) (DTNB) releasing thionitro-benzoic acid, which indicated that the selenium in the conjugate is present as selenol. However, the reaction rate of the conjugate was slower than cysteine which may be due to partially restricted access of DTNB to the selenol group in the conjugate. This conjugate had 1,1-diphenyl-2-picryl-hydrazyl(DPPH) radical scavenging activity as well as superoxide anion scavenging activity. These results indicate that the conjugate serves as a useful model compound with a stable selenol group having a range of biological activities, and suggest a possible antioxidant defensive role for the complex of endogenous heparin-like substance and selenoprotein P.