Comparative biochemical studies of carotenoids in fishes--XXIX. Isolation of new luteins, lutein F and lutein G from marine fishes

New luteins, lutein F [(3R,3'R,6'S)-beta,epsilon-carotene-3, 3'-diol] and lutein G [(3S,3'R,6'S)-beta,epsilon-carotene-3,3'-diol] have been isolated from marine fishes.     

Lead optimization of 5-amino-6-(2,2-dimethyl-5-oxo-4-phenylpiperazin-1-yl)-4-hydroxyhexanamides to reduce a cardiac safety issue: Discovery of DS-8108b,an orally active renin inhibitor

With the aim to address an undesired cardiac issue observed with our related compound in the recently disclosed novel series of renin inhibitors, further chemical modifications of this series were performed. Extensive structure–activity relationships studies as well as in vivo cardiac studies using the electrophysiology rat model led to the discovery of clinical candidate trans-adamantan-1-ol analogue 56 (DS-8108b) as a potent renin inhibitor with reduced potential cardiac risk. Oral administration of single doses of 3 and 10 mg/kg of 56 in cynomolgus monkeys pre-treated with furosemide led to significant reduction of mean arterial blood pressure for more than 12 h.     

Conformational Change of a Natto Mucin in Solution

The mucin obtained from a natto sample was found to be composed of 58 % of γ-polyglutamic acid and 40% of polysaccharide. The ratio of l- and d-glutamic acid was determined to be 58:42 using l-glutamic acid decarboxylase. The weight- and z-average molecular weight were 2.08 × 10⁵ and 2.22 × 10⁵, respectively. The distribution curve of the sedimentation coefficient showed a small heterogeneity. The mucin molecule was considered to be randomly coiled at pH 5.0 ~ 8.8 and to be a rod-like molecule in the lower pH region.     

Galnt3 deficiency disrupts acrosome formation and leads to oligoasthenoteratozoospermia

Galnt3 belongs to the GalNAc transferase gene family involved in the initiation of mucin-type O-glycosylation. Male Galnt3-deficient (Galnt3 ^?/?) mice were infertile, as previously reported by Ichikawa et al. (2009). To investigate the involvement of Galnt3 in spermatogenesis, we examined the differentiation of germ cells in Galnt3 ^?/? mice. Galnt3 mRNA was most highly expressed in testis, and Galnt3 protein was localized in the cis-medial parts of the Golgi stacks of spermatocytes and spermatids in the seminiferous tubules. Spermatozoa in Galnt3 ^?/? mice were rare and immotile, and most of them had deformed round heads. They exhibited abnormal acrosome and disturbed mitochondria arrangement in the flagella. At the cap phase, proacrosomal vesicles of various sizes, which had not coalesced to form a single acrosomal vesicle, were attached to the nucleus in Galnt3 ^?/? mice. TUNEL-positive cells were increased in the seminiferous tubules. The binding of VVA lectin, which recognizes the Tn antigen (GalNAc-O-Ser/Thr), in the acrosomal regions of spermatids and spermatozoa in Galnt3 ^?/? mice was drastically reduced. Equatorin is a N, O-sialoglycoprotein localized in the acrosomal membrane and is suggested to be involved in sperm–egg interaction. Immunohistochemical and Western blot analyses showed a drastic reduction in the reactivity with MN9 antibody, which recognizes the O-glycosylated moiety of equatorin and inhibits sperm–egg interaction. These findings indicate that deficiency of Galnt3 results in a severe reduction of mucin-type O-glycans in spermatids and causes impaired acrosome formation, leading to oligoasthenoteratozoospermia, and suggest that Galnt3 may also be involved in the process of fertilization through the O-glycosylation of equatorin.     

Practical one-step glucuronidation via biotransformation

We herein report a practical one-step glucuronidation method by biotransformation using Streptomyces sp. SANK 60895. This novel direct method of biotransformation has been shown to be more practical and scalable for glucuronidation than previously reported chemical and enzymatic procedures given its simplicity, high β-selectivity, cost-effectiveness, and reproducibility. We applied the present method to the synthesis of acyl glucuronide and hydroxy-β-glucuronide of mycophenolic acid and compound 4, respectively. This method was also shown to be applicable to the N-glucuronidation of various compounds.