Prokaryotic transcriptional regulatory elements have been adopted for controlled expression of cloned genes in mammalian cells and animals, the cornerstone for gene-function correlations, drug discovery, biopharmaceutical manufacturing as well as advanced gene therapy and tissue engineering. Many prokaryotes have evolved specific molecular communication systems known as quorum-sensing to coordinate population-wide responses to physiological and/or physicochemical signals. A generic bacterial quorum-sensing system is based on a diffusible signal molecule that prevents binding of a repressor to corresponding operator sites thus resulting in derepression of a target regulon. In Streptomyces, a family of butyrolactones and their corresponding receptor proteins, serve as quorum-sensing systems that control morphological development and antibiotic biosynthesis. Fusion of the Streptomyces coelicolor quorum-sensing receptor (ScbR) to a eukaryotic transactivation domain (VP16) created a mammalian transactivator (SCA) which binds and adjusts transcription from chimeric promoters containing an SCA-specific operator module (P(SPA)). Expression of erythropoietin or the human secreted alkaline phosphatase (SEAP) by this quorum-sensor-regulated gene expression system (QuoRex) could be fine-tuned by non-toxic butyrolactones in a variety of mammalian cells including human primary and mouse embryonic stem cells. Following intraperitoneal implantation of microencapsulated Chinese hamster ovary cells transgenic for QuoRex-controlled SEAP expression into mice, the serum levels of this model glycoprotein could be adjusted to desired concentrations using different butyrolactone dosing regimes.

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Analogs of naturally occurring furanones that were reported to be weak inhibitors of Serratia marcescens chitinases were prepared and tested towards various chitinases. Some of these compounds -but not the natural products -were found to be weak but selective inhibitors; all glycosylated analogs tested were inactive. Activation of the plant enzyme hevamine was observed in one case, which is unusual.The polysaccharide chitin is depolymerized in nature by chitinases [EC 3.2.1.14] belonging to the glycosidase families 18 and 19. 1 Family 18 chitinases are widely distributed in mammals, arthropods, nematodes, protozoa, plants, fungi, bacteria, and viruses, whereas family 19 chitinases only occur in plants and in addition also in Streptomyces. Besides their role as digestive enzymes and as defense mechanisms, chitinases play important roles in the regulation of growth and development of many organisms (for a review, see ref. 2 ).Selective inhibition of chitinases is an attractive target for the development of antifungal agents, parasiticides, and insecticides for agricultural and medical applications. Up to now, the most potent inhibitor of chitinases is allosamidin (1), which shows remarkable species selectivity, as revealed by IC 50 values ranging from 0.0002 mM to 20.9 mM (for a review, see 3 ). The recent finding of a cyclic peptide as a potent inhibitor 4 demonstrates that quite different chemical compounds might be suited as chitinase inhibitors, but both allosamidin (1) and this peptide are too complicated to allow a large-scale synthesis and in addition, at least allosamidin (1) is unstable under field conditions. The design of new chitinase inhibitors avoiding these problems is therefore a challenge.We present here compounds (Figure 1, Scheme 2) that were synthesized after finding that the butenolides 2a and 3a, which were isolated from the fermentation broth of Streptomyces antibioticus TÜ 99, showed some activity as inhibitors of the chitinase of Serratia marcescens in preliminary tests. 5

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