Dudawalamides A−D, Antiparasitic Cyclic Depsipeptides from the Marine Cyanobacterium Moorea producens

HPLC. DudA family of 2,2-dimethyl-3-hydroxy-7-octynoic acid (Dhoya)-containing cyclic depsipeptides, named dudawalamides A−D (1−4), was isolated from a Papua New Guinean field collection of the cyanobacterium Moorea producens using bioassay-guided and spectroscopic approaches. The planar structures of dudawalamides A−D were determined by a combination of 1D and 2D NMR experiments and MS analysis, whereas the absolute configurations were determined by X-ray crystallography, modified Marfey’s analysis, chiral-phase GCMS, and chiral-phase awalamides A−D possess a broad spectrum of antiparasitic activity with minimal mammalian cell cytotoxicity. Comparative analysis of the Dhoya-containing class of lipopeptides reveals intriguing structure−activity relationship features of these NRPS−PKS-derived metabolites and their derivatives.HPLC. DudA family of 2,2-dimethyl-3-hydroxy-7-octynoic acid (Dhoya)-containing cyclic depsipeptides, named dudawalamides A−D (1−4), was isolated from a Papua New Guinean field collection of the cyanobacterium Moorea producens using bioassay-guided and spectroscopic approaches. The planar structures of dudawalamides A−D were determined by a combination of 1D and 2D NMR experiments and MS analysis, whereas the absolute configurations were determined by X-ray crystallography, modified Marfey’s analysis, chiral-phase GCMS, and chiral-phase awalamides A−D possess a broad spectrum of antiparasitic activity with minimal mammalian cell cytotoxicity. Comparative analysis of the Dhoya-containing class of lipopeptides reveals intriguing structure−activity relationship features of these NRPS−PKS-derived metabolites and their derivatives

Credneramides A and B: Neuromodulatory Phenethylamine and Isopentylamine Derivatives of a Vinyl Chloride-Containing Fatty Acid from cf. Trichodesmium sp. nov.

Credneramides A (1) and B (2), two vinyl chloride-containing metabolites, were isolated from a Papua New Guinea collection of cf. Trichodesmium sp. nov. and expand a recently described class of vinyl chloride-containing natural products. The precursor fatty acid, credneric acid (3), was isolated from both the aqueous and organic fractions of the parent fraction as well as from another geographically and phylogenetically distinct cyanobacterial collection (Panama). Credneramides A and B inhibited spontaneous calcium oscillations in murine cerebrocortical neurons at low micromolar concentrations (1, IC 50 4.0 μM; 2, IC 50 3.8 μM).Credneramides A (1) and B (2), two vinyl chloride-containing metabolites, were isolated from a Papua New Guinea collection of cf. Trichodesmium sp. nov. and expand a recently described class of vinyl chloride-containing natural products. The precursor fatty acid, credneric acid (3), was isolated from both the aqueous and organic fractions of the parent fraction as well as from another geographically and phylogenetically distinct cyanobacterial collection (Panama). Credneramides A and B inhibited spontaneous calcium oscillations in murine cerebrocortical neurons at low micromolar concentrations (1, IC 50 4.0 μM; 2, IC 50 3.8 μM)

Borderline personality features possibly related to cingulate and orbitofrontal cortices dysfunction due to schizencephaly.

Prefrontal cortex dysfunction has been associated with a series of behavioral symptoms, such as impulsivity and affective instability, which are the defining features of several personality disorders, notably, borderline personality disorder. We report on a 27-year-old patient with schizencephaly in the right frontal lobe (cingulate cortex lesion and secondary orbitofrontal cortex dysfunction) presenting with prominent borderline features and compromise of executive functions, decision-making and attention. We hypothesize that the personality disorder of our patient could be related to cingulate cortex lesion and secondary orbitofrontal cortex dysfunction associated with schizencephaly

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Structure elucidation of biomedically relevant marine cyanobacterial natural products

The use of natural products for the treatment of disease has been an age-old practice. With chemical diversity, structural complexity, and perceived ecologic roles in chemical defense, natural products, not surprisingly, continue to serve as inspiration for pharmaceutical lead compounds. In that spirit, this dissertation further delineates the novel chemistry of marine natural products by describing bioassay-guided isolation and structure elucidation of cyanobacterial secondary metabolites with efficacy against several targets of human disease. Chapter I presents a rationale for the dissertation research by providing a general introduction of marine natural products chemistry and drug development as it relates specifically to cyanobacteria. Chapter II describes the isolation, structure elucidation, and anti-inflammatory activity of malyngamide 2, a nitric oxide inhibitor. Chapter III explores bioassay-guided fractionation and structure elucidation of hoiamide D, a cyanobacterial derived inhibitor of p53/MDM2 interaction, an attractive target for anti-cancer drug development. Chapter IV describes the isolation and structure elucidation of the credneramides, neuromodulatory vinyl chloride-containing fatty acid amides of a new cyanobacterial species. This chapter also explores the evolution, taxonomy, and biosynthetic source of the credneramides. Chapter V expounds upon the growing class of cyanobacterial depsipeptides containing the unique DHOYA (3-hydroxy-2,2- dimethyl-7-octynoic acid) unit by describing the isolation, structure elucidation, and anti-parasitic activity of dudawalamide E and naopopeptin, a closely related HMOYA (3 -hydroxy-2-methyl-7-octynoic acid) containing natural product. Chapter VI provides concluding thoughts with perspective on the future of marine natural products chemistr

Dudawalamides A–D, Antiparasitic Cyclic Depsipeptides from the Marine Cyanobacterium <i>Moorea producens</i>

A family of 2,2-dimethyl-3-hydroxy-7-octynoic acid (Dhoya)-containing cyclic depsipeptides, named dudawalamides A–D (<b>1</b>–<b>4</b>), was isolated from a Papua New Guinean field collection of the cyanobacterium <i>Moorea producens</i> using bioassay-guided and spectroscopic approaches. The planar structures of dudawalamides A–D were determined by a combination of 1D and 2D NMR experiments and MS analysis, whereas the absolute configurations were determined by X-ray crystallography, modified Marfey’s analysis, chiral-phase GCMS, and chiral-phase HPLC. Dudawalamides A–D possess a broad spectrum of antiparasitic activity with minimal mammalian cell cytotoxicity. Comparative analysis of the Dhoya-containing class of lipopeptides reveals intriguing structure–activity relationship features of these NRPS–PKS-derived metabolites and their derivatives

Credneramides A and B: Neuromodulatory Phenethylamine and Isopentylamine Derivatives of a Vinyl Chloride-Containing Fatty Acid from cf. Trichodesmium sp nov.

Credneramides A (1) and B (2), two vinyl chloride-containing metabolites, were isolated from a Papua New Guinea collection of cf. Trichodesmium sp. nov. and expand a recently described class of vinyl chloride-containing natural products. The precursor fatty acid, credneric acid (3), was isolated from both the aqueous and organic fractions of the parent fraction as well as from another geographically and phylogenetically distinct cyanobacterial collection (Panama). Credneramides A and B inhibited spontaneous calcium oscillations in murine cerebrocortical neurons at low micro-molar concentrations (1, IC50 4.0 mu M; 2, IC50 3.8 mu M).NIH [NS 053398, ICBG FIC TW006634]NI

Credneramides A and B: Neuromodulatory Phenethylamine and Isopentylamine Derivatives of a Vinyl Chloride-Containing Fatty Acid from cf. <i>Trichodesmium</i> sp. nov.

Credneramides A (<b>1</b>) and B (<b>2</b>), two vinyl chloride-containing metabolites, were isolated from a Papua New Guinea collection of cf. <i>Trichodesmium</i> sp. nov. and expand a recently described class of vinyl chloride-containing natural products. The precursor fatty acid, credneric acid (<b>3</b>), was isolated from both the aqueous and organic fractions of the parent fraction as well as from another geographically and phylogenetically distinct cyanobacterial collection (Panama). Credneramides A and B inhibited spontaneous calcium oscillations in murine cerebrocortical neurons at low micromolar concentrations (<b>1</b>, IC₅₀ 4.0 μM; <b>2</b>, IC₅₀ 3.8 μM)