Chemical mediators are key compounds for controlling symbiotic interactions in the environment.Here, we disclose a fully stereoselective total synthesis of the algae differentiation factor (À )-thallusin that utilizes sophisticated 6-endo-cyclization chemistry and effective late-stage sp 2 -sp 2 -couplings using non-toxic reagents. An EC 50 of 4.8 pM was determined by quantitative phenotype profiling in the green seaweed Ulva mutabilis (Chlorophyte), underscoring this potent mediator's enormous, pan-species bioactivity produced by symbiotic bacteria. SAR investigations indicate that (À )-thallusin triggers at least two different pathways in Ulva that may be separated by chemical editing of the mediator compound structure.

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Abstract. A 1,2,3-triazole-based RGD peptidomimetic having nanomolar affinity for αvβ3 integrin was conjugated to the potent antimitotic paclitaxel via an oxime heterobifunctional linker. The resulting construct maintained nanomolar binding concentration to αvβ3 integrin and showed 11-fold selectivity in terms of cytotoxicity towards highly αvβ3 expressing U87MG cancer cells relative to non αvβ3 expressing MCF7 cells, indicating promising cancer cell targeting capacity. RGD, peptidomimetic, integrin, paclitaxel, click, cytotoxicity, cancer The efficacy of chemotherapeutic agents clinically used for the treatment of malignant tumours is generally limited by their non-specific toxicity against off-target cells, especially those characterised by a high proliferation rate, resulting in a reduced therapeutic index and serious side effects (e.g. alopecia, nausea, vomiting and immunosuppression). Several strategies have been developed over the years in order to overcome these problems and achieve a tumour-targeted delivery of cytotoxic agents. 1 An attractive approach is represented by hybrid compounds, containing a cytotoxic drug bound to a moiety that specifically identifies protein markers overexpressed on cancer cells. Thanks to the development of phage display technologies, several peptide sequences capable of recognising tumour markers have been discovered and extensively investigated as valuable tools for tumour-targeted delivery of chemotherapeutics. 1-2 RGD-containing peptides targeting αvβ3 integrin belong to this class of tumourhoming vectors. The overexpression of αvβ3 on solid tumours, along with its capacity to be internalised via endocytosis after binding of ligands such as RGD peptides, makes it an attractive target for tumour delivery of anticancer agents. 3 A number of cytotoxic drugs have been conjugated to tumour-homing peptides containing the RGD motif and the resulting constructs assessed in animal models. Several studies in this field provided experimental evidence that RGDbased strategies contribute to reduce the toxicity and augment the therapeutic window of existing chemotherapeutics. 1,4,5 Key words

A multiblocked mutant strain (ΔAHBA and Δasm12, asm21) of Actinosynnema pretiosum, the producer of the highly toxic maytansinoid ansamitocin, has been used for the mutasynthetic production of new proansamitocin derivatives. The use of mutant strains that are blocked in the biosynthesis of an early building block as well as in the expression of two tailoring enzymes broadens the scope of chemo-biosynthetic access to new maytansinoids. Remarkably, a ring-expanded macrolactone derived from ansamitocin was created for the first time.