The endoglycosidase hydrolase Hyaluronidase 1 (Hyal‑1) is one of five functional hyaluronidases in human body. Degradation of high molecular weight hyaluronan (HA) is mainly catalyzed by Hyal-1 into smaller fragments. These fragments have inflammatory and angiogenic effects.¹ The role of Hyal-1 in cancer progression, e. g prostate or bladder, has been discussed for a long time. In several cancer cells, the expression level of Hyal-1 was elevated in comparison to not malignant cells, resulting in higher Hyal‑1 activity and tumor progression.^2,3 Although Hyal‑1 is an interesting target for pharmaceutical purposes, no potent inhibitors have been found so far. The enzyme source seems to be the bottleneck in investigation of potent inhibitors. Production of active Hyal‑1 is one of the most challenging tasks. Eukaryotic extraction and purification is very time consuming and expensive. Recombinant expression in bacteria leads to inactive Hyal-1 forming inclusion bodies. Therefore, potent Hyal-1 inhibitors, like chemical compounds or plant extracts, are routinely screened against bovine testis hyaluronidase, which has an amino acid sequence identity of approx. 40 % compared to human Hyal‑1. This again causes problems in interpretation of the obtained data, development of a pharmacophore model or searching for leader compounds inhibiting human Hyal‑1. Using Autodisplay technology, we are able to express human Hyal-1 on the surface of Escherichia coli in an active form.⁴ With this system, it is possible to screen compounds, directly using the desired target. A combination of pharmacophore modeling followed by docking studies using a virtual system, helped us to get first impressions about binding of the substances to Hyal-1. Next, screening the best hits with whole-cells displaying Hyal-1 seems to be a promising way to find the needle in the haystack.

References                                                                                                                                                                                        

1. Stern, R. Semin Cancer Biol. 2008, 18, 275-280
2. Lokeshwar, V.B.; Obek C.; Pham H. T.; Wei D; Young M. J.; Duncan R.C.; Soloway M. S.; Block N. L. J Urol, 2000, 163, 348-356.
3. Lokeshwar, V. B.; Rubinowczi D.; Schroeder G. L.; Forgacs E.; Minna J. D.; Block N. L.; Nadji M.; Lokeshwar B. L. J Biol Chem, 2001, 276, 11922-11932.
4. Orlando Z.; Lengers I.; Melzig M. F.; Buschauer A.; Hensel A.; Jose J. Molecules, 2015, 20, 15449-15498.