Additional file 1: of Daptomycin, a last-resort antibiotic, binds ribosomal protein S19 in humans

Supplementary data (synthetic routes, 1H NMR and MS/MS spectra of reported compounds, supplementary figures and tables) associated with this article can be found, in the online version, at http://[…]. (PDF 2959 kb

The Role of Different Structural Motifs in the Ultrafast Dynamics of Second Generation Protein Stains

Engineering the properties of fluorescent probes through modifications of the fluorophore structure has become a subject of interest in recent times. By doing this, the photophysical and photochemical properties of the modified fluorophore can be understood and this can guide the design and synthesis of better fluorophores for use in biotechnology. In this work, the electronic spectra and fluorescence decay kinetics of four analogues of the fluorescent natural product epicocconone were investigated. Epicocconone is unique in that the native state is weakly green fluorescent, whereas the enamine formed reversibly with proteins is highly emissive in the red. It was found that the ultrafast dynamics of the analogues depends profoundly on the H-bonding effect of solvents and solvent viscosity though solvent polarity also plays a role. Comparing the steady state and time-resolved data, the weak fluorescence of epicocconone in its native state is most likely due to the photoisomerization of the hydrocarbon side chain, while the keto enol moiety also has a role to play in determining the fluorescence quantum yield. This understanding is expected to aid the design of better protein stains from the same family

Banksialactones and Banksiamarins: Isochromanones and Isocoumarins from an Australian Fungus, <i>Aspergillus banksianus</i>

Chemical investigation of an Australian fungus, <i>Aspergillus banksianus</i>, led to the isolation of the major metabolite banksialactone A (<b>1</b>), eight new isochromanones, banksialactones B–I (<b>2</b>–<b>9</b>), two new isocoumarins, banksiamarins A and B (<b>10</b> and <b>11</b>), and the reported compounds, clearanol I (<b>12</b>), dothideomynone A (<b>13</b>), questin (<b>14</b>), and endocrocin (<b>15</b>). The structures of <b>1</b>–<b>11</b> were established by NMR spectroscopic data analysis, and the absolute configurations were determined from optical rotations and ECD spectra in conjunction with TD-DFT calculations. The secondary metabolite profile of <i>A. banksianus</i> is unusual, with the 11 most abundant metabolites belonging to a single isochromanone class. Conjugation of <b>1</b> with endocrocin, 5-methylorsellinic acid, 3,5-dimethylorsellinic acid, mercaptolactic acid, and an unknown methylthio source gave rise to five unprecedented biosynthetic hybrids, <b>5</b>–<b>9</b>. The isolated compounds were tested for cytotoxicity, antibacterial, and antifungal activities, with hybrid metabolites <b>7</b>–<b>9</b> displaying weak cytotoxic and antibiotic activities

Design and Synthesis of Epicocconone Analogues with Improved Fluorescence Properties

Epicocconone is a natural latent fluorophore that is widely used in biotechnology because of its large Stokes shift and lack of fluorescence in its unconjugated state. However, the low photostability and quantum yields of epicocconone have limited its wider use, and in the absence of a total synthesis, this limitation has been a long-standing problem. Here we report a general strategy for the synthesis of epicocconone analogues that relies on a 2-iodoxybenzoic acid-mediated dearomatization and on the replacement of the triene tail of the natural product by an aromatic ring. This design element is general and the synthesis is straightforward, providing ready access to libraries of polyfunctional fluorophores with long Stokes shifts based on the epicocconone core. Our structural modifications resulted in analogues with increased photostability and quantum yields compared with the natural product. Staining proteomic gels with these new analogues showed significant lowering of the detection limit and a 30% increase in the number of low-abundance proteins detected. These epiccoconone analogues will substantially improve the discovery rate of biomarker needles in the proteomic haystack