Potent, selective and broadly characterized small molecule modulators of protein function (chemical probes) are powerful research reagents. The pharmaceutical industry has generated many high-quality chemical probes and several of these have been made available to academia. However, probe-associated data and control compounds, such as inactive structurally related molecules and their associated data, are generally not accessible. The lack of data and guidance makes it difficult for researchers to decide which chemical tools to choose. Several pharmaceutical companies (AbbVie, Bayer, Boehringer Ingelheim, Janssen, MSD, Pfizer, and Takeda) have therefore entered into a pre-competitive collaboration to make available a large number of innovative high-quality probes, including all probe-associated data, control compounds and recommendations on use (https://openscienceprobes.sgc-frankfurt.de/). Here we describe the chemical tools and target-related knowledge that have been made available, and encourage others to join the project.

DdLimE regulates cell motility and cytokinesis in Dictyostelium. To specify its function, we generated knock-out mutants and analyzed mitosis by marking the mitotic apparatus with GFP-alpha-tubulin. Characteristic of DdLimE-null cells is a late reversal of cytokinesis caused by backward movement of the incipient daughter cells. This process of "retro-cytokinesis" is accompanied by a delay in disassembly of the mitotic spindle. The length of interphase microtubules is increased and their depolymerization at prophase is impaired. These data indicate that DdLimE links the cortical actin network, where it is located, to the microtubule system, whose dynamics it regulates.

The efficacy of the widely used chemotherapeutic drug cisplatin is limited by the occurrence of drug-resistant tumour cells. To fully exploit the potential of this drug in cancer therapy, it is imperative to understand the molecular basis of cisplatin resistance. Using an insertional mutagenesis technique in cells of Dictyostelium discoideum, we have identified six genes which are involved in cisplatin resistance. None of these genes has been previously linked to resistance to this drug. Several of these genes encode proteins that are involved in signal transduction pathways which regulate cell death, cell proliferation or gene regulation. The resistance of these mutant strains is specific for cisplatin, since deletion of these genes does not confer resistance to other DNA-damaging agents. Significantly, the disruption of three of these genes, encoding the sphingosine-1-phosphate lyase, the RegA cAMP phosphodiesterase and a phosphatidylinositol-4-phosphate 5-kinase, also results in abnormalities in the multicellular development of this organism, although there is no change in the rate of mitotic cell growth. This study has identified previously unsuspected molecular pathways which function in the cellular response to cisplatin and are required for normal morphogenesis, and underscores the complexity of the cellular response to cisplatin. These pathways provide potential targets for modulating the response to this important drug.

Reaction of fullerene-Cso with an excess of BH3-THF complex followed by hydrolysis with either glacial acetic acid, sodium hydroxide/hydrogen peroxide or sodium hydroxide gives water soluble fullerols; oxidation of initially formed C-H bonds is believed to accompany the reaction.Fullerenes are closed cage alkenes capable of undergoing a wide variety of additions. 1 The attachment of hydroxy groups to f ~l 1 e r e n e -C ~~ by various methods was described recently,2.3 and involved: (a) reaction with mixed nitric acid-sulfuric acid followed by basic work-up (believed to involve nucleophilic substitution by O H of the initial nitronium adduct); ( b ) reaction with nitronium borofluoride and a carboxylic acid, followed by basic hydrolysis of the nitro-organocarboxylated fullerene intermediate; (c) hydrolysis of epoxides formed by reaction of f ~1 l e r e n e -C ~~ with MCPBA; ( d ) reaction with solid KOH under vacuum. The IR spectra of the products obtained under conditions (a) and (b) are reproduced in Figs. l(a) and l(b); notable features include the absence of C-H stretching bands (consistent with the expected product), and the strong broad absorptions at 3424, 1595, 1392, 1084, ca. 470 cm-1 [conditions ( a ) ] , and 3432, 1590, 1380, 1045, and 600 cm-1 [conditions ( b ) ] . LSIMS mass spectrometry indicated that up to ca. thirty hydroxy groups may be attached to the cage, although the average incorporation was about twenty.As part of an investigation of additions to fullerenes we studied hydroboration of fullerene-Cm, using an excess of BH3-THF. Given the normal behaviour of organoboranes, we anticipated that the intermediate would react with H202-NaOH to produce fullerene-C60 possessing adjacent H and O H groups, and that treatment with HOAc would generate extensively hydrogenated fullerene-Ca. We were encouraged in this latter expectation by the report that reaction of 2 equiv. of BH3-THF with fullerene-C60 followed by decomposition by HOAc gave CaH2,4 a result which we readily reproduced. However, the outcome of our experiments was unexpected; both reactions give a product which is effectively identical to that obtained from the hydroxylations (a)-(c) described above. The implication is that C-H bonds on the fullerene cage are readily oxidised to C-OH bonds. We believe that allylic oxidation (known to be catalysed by single oxygen,s of which fullerene-C60 is a potent producer6 may occur subsequent to initial formation of the C-H bond. This conclusion I