Research Overview of the Laboratory of Analytical Bioorganic Chemistry

The laboratory of analytical bioorganic chemistry drastically changed its research projects in 2005. Some of the recent achievements are described

Wavefunction Analysis of STM Image: Surface Reconstruction of Organic Charge Transfer Salts

In this chapter, the wavefunction analysis is demonstrated, applied to the organic charge transfer salts composed of electron donor and electron acceptor molecules. Scanning tunneling microscopy (STM) images of the surface donor layers in the three charge transfer salts, α-(BEDT-TTF)2I3, β-(BEDT-TTF)2I3, and (EDO-TTF)2PF6, are analyzed with the atomic π electron orbitals of sulfur, oxygen, and carbon atoms. We have deduced three different kinds of surface molecular reconstructions as follows: (1) charge redistribution in α-(BEDT-TTF)2I3, (2) translational reconstruction up to 0.1 nm in β-(BEDT-TTF)2I3, and (3) rotational reconstruction transforming the 1D axis from the a axis to the b axis in (EDO-TTF)2PF6. Finally, it is concluded that the surface reconstruction is ascribed to the additional gain of the cohesive energy of the π electron system, provoked by the reduced steric hindrance with the anions of the missing outside double layer. The investigations of the surface states provide not only interesting behaviors of the surface cation layer, but also important insights into the electronic states of a lot of similar charge transfer crystals, as demonstrated in α-(BEDT-TTF)2I3

Aerobic H2 production related to formate metabolism in white-rot fungi

Biohydrogen is mainly produced by anaerobic bacteria, anaerobic fungi, and algae under anaerobic conditions. In higher eukaryotes, it is thought that molecular hydrogen (H2) functions as a signaling molecule for physiological processes such as stress responses. Here, it is demonstrated that white-rot fungi produce H2 during wood decay. The white-rot fungus Trametes versicolor produces H2 from wood under aerobic conditions, and H2 production is completely suppressed under hypoxic conditions. Additionally, oxalate and formate supplementation of the wood culture increased the level of H2 evolution. RNA-seq analyses revealed that T. versicolor oxalate production from the TCA/glyoxylate cycle was down-regulated, and conversely, genes encoding oxalate and formate metabolism enzymes were up-regulated. Although the involvement in H2 production of a gene annotated as an iron hydrogenase was uncertain, the results of organic acid supplementation, gene expression, and self-recombination experiments strongly suggest that formate metabolism plays a role in the mechanism of H2 production by this fungus. It is expected that this novel finding of aerobic H2 production from wood biomass by a white-rot fungus will open new fields in biohydrogen research

Protein S-guanylation by the biological signal 8-nitroguanosine 3\u27,5\u27-cyclic monophosphate

The signaling pathway of nitric oxide (NO) depends mainly on guanosine 3′,5′-cyclic monophosphate (cGMP, 1). Here we report the formation and chemical biology of a nitrated derivative of cGMP, 8-nitroguanosine 3′,5′-cyclic monophosphate (8-nitro-cGMP, 2), in NO-mediated signal transduction. Immunocytochemistry demonstrated marked 8-nitro-cGMP production in various cultured cells in an NO-dependent manner. This finding was confirmed by HPLC plus electrochemical detection and tandem mass spectrometry. 8-Nitro-cGMP activated cGMP-dependent protein kinase and showed unique redox-active properties independent of cGMP activity. Formation of protein Cys-cGMP adducts by 8-nitro-cGMP was identified as a new post-translational modification, which we call protein S-guanylation. 8-Nitro-cGMP seems to regulate the redox-sensor signaling protein Keap1, via S-guanylation of the highly nucleophilic cysteine sulfhydryls of Keap1. This study reveals 8-nitro-cGMP to be a second messenger of NO and sheds light on new areas of the physiology and chemical biology of signal transduction by NO

Bioactive Alkaloids from the Sea: A Review

In our ongoing search for bioactive substances from marine organisms, novel alkaloids have been isolated. Pinnatoxins and pinnamine, potent shellfish poisons, were purified from the Okinawan bivalve Pinna muricata. Pinnatoxins activate Ca2+ channels. Halichlorine was isolated from the marine sponge Halichondria okadai. This compound inhibits the induction of VCAM-1. Drugs that block VCAM-1 may be useful for treating coronary artery diseases, angina, and noncardiovascular inflammatory diseases. Pinnaic acids, which are cPLA2 inhibitors, were also obtained from P. muricata. Interestingly, the structures of pinnaic acids are closely related to that of halichlorine. Norzoanthamine hydrochloride, isolated from the colonial zoanthid Zoanthus sp., suppresses decreases in bone weight and strength in ovariectomized mice, and could be a good candidate for an osteoporotic drug. Ircinamine, purified from the marine sponge Ircinia sp., has a reactive thioester. Aburatubolactams, inhibitors of superoxide anion generation, were isolated from Streptomyces sp. This article covers the bioactive marine alkaloids that have been recently isolated by this research group