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.

Urotensin-II (U-II) receptors are widely distributed in the central nervous system. Intracerebroventricular (i.c.v.) injection of U-II causes hypertension and bradycardia and stimulates prolactin and thyrotropin secretion. However, the behavioral effects of centrally administered U-II have received little attention. In the present study, we tested the effects of i.c.v. injections of U-II on behavioral, metabolic, and endocrine responses in mice. Administration of graded doses of U-II (1-10,000 ng/mouse) provoked: (1) a dose-dependent reduction in the number of head dips in the hole-board test; (2) a dose-dependent reduction in the number of entries in the white chamber in the black-and-white compartment test, and in the number of entries in the central platform and open arms in the plus-maze test; and (3) a dose-dependent increase in the duration of immobility in the forced-swimming test and tail suspension test. Intracerebroventricular injection of U-II also caused an increase in: food intake at doses of 100 and 1,000 ng/mouse, water intake at doses of 100-10,000 ng/mouse, and horizontal locomotion activity at a dose of 10,000 ng/mouse. Whatever was the dose, the central administration of U-II had no effect on body temperature, nociception, apomorphine-induced penile erection and climbing behavior, and stress-induced plasma corticosterone level. Taken together, the present study demonstrates that the central injection of U-II at doses of 1-10,000 ng/mouse induces anxiogenic- and depressant-like effects in mouse. These data suggest that U-II may be involved in some aspects of psychiatric disorders.

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