Sulphated oligosaccharides as inhibitors of hyaluronidases from bovine testis, bee venom and Streptococcus agalactiae

Abstract Potent and specific inhibitors of hyaluronidases, a group of enzymes preferentially catalysing the hydrolysis of hyaluronic acid, are not known so far. Such compounds could be useful as pharmacological tools for studying the physiological and pathophysiological role of both hyaluronan and hyaluronidases. The effects of sulphated and non-sulphated structurally different oligosaccharides on bovine testicular hyaluronidase, hyaluronidase from bee venom and hyaluronate lyase from STREPTOCOCCUS AGALACTIAE (hylB 4755 ) were studied with the Morgan-Elson reaction. Several active compounds were identified within a series of sulphated β-(1,4)-galacto-oligosaccharides. The determined IC 50 values of these sulphated oligosaccharides ranged from 4 μM to 630 μM for all hyaluronan-degrading enzymes. Sulphated oligosaccharides like verbascose, planteose and neomycin showed comparable inhibition on all hyaluronidases, thereby possessing 100 - 500 times the activity of the widely accepted hyaluronidase inhibitor apigenin.