5,7-Diphenyl-3-ureidohexahydroazepin-2-ones as Cholecystokinin-B receptor ligands

A series of 5,7-diphenyl-3-ureidohexahydroazepin-2-one cholecystokinin-B (CCK-B) receptor antagonists was synthesized using Beckmann ring expansion of a suitable 2,4-diphenylcyclohexanone as a key step. SAR studies revealed the importance of the 5-aryl group for high and selective CCK-B receptor affinity, as illustrated in compound (−)-10i (CCK-B IC₅₀ = 6.8 nM).     

Isolation and Refined Regional Mapping of Expressed Sequences from Human Chromosome 21

To increase candidate genes from human chromosome 21 for the analysis of Down syndrome and other genetic diseases localized on this chromosome, we have isolated and studied 9 cDNA clones encoded by chromosome 21. For isolating cDNAs, single-copy microclones from a chromosome 21 microdissection library were used in direct screening of various cDNA libraries. Seven of the cDNA clones have been regionally mapped on chromosome 21 using a comprehensive hybrid mapping panel comprising 24 cell hybrids that divide the chromosome into 33 subregions. These cDNA clones with refined mapping positions should be useful for identification and cloning of genes responsible for the specific component phenotypes of Down syndrome and other diseases on chromosome 21, including progressive myoclonus epilepsy in 21q22.3.     

The evolution of pathways for aromatic hydrocarbon oxidation inPseudomonas

The organisation and nucleotide sequences coding for the catabolism of benzene, toluene (and xylenes), naphthalene and biphenylvia catechol and the extradiol (meta) cleavage pathway inPseudomonas are reviewed and the various factors which may have played a part in their evolution are considered. The data suggests that the complete pathways have evolved in a modular way probably from at least three elements. The commonmeta pathway operons, downstream from the ferredoxin-like protein adjacent to the gene for catechol 2,3-dioxygenase, are highly homologous and clearly share a common ancestry. This common module may have become fused to a gene or genes the product(s) of which could convert a stable chemical (benzoate, salicylate, toluene, benzene, phenol) to catechol, thus forming the lower pathway operons found in modern strains. The upper pathway operons might then have been acquired as a third module at a later stage thus increasing the catabolic versatility of the host strains.     

NADH-Linked Ferricyanide and Cytochrome c Reduction Activities in Corn Root Plasma Membrane

Corn root plasma membrane catalyzed NADH reduction of ferricyanideand cytochrome c over a wide pH range. At pH 7.5, apparent K_msof NADH-cytochrome c pair were significantly lower than thoseof NADH-ferricyanide pair. FMN and polylysine respectively enhancedthe reduction of ferricyanide and cytochrome c. Yet, polyaspartatedecreased the ferricyanide reduction. NADH oxidation observedin the presence of both ferricyanide and cytochrome c was significantlyslower than the sum of rates obtained with individual acceptors.The results suggest that the membrane may contain differentbut not totally independent reduction sites for cytochrome cand ferricyanide. (Received April 13, 1993; Accepted August 23, 1993)     

Regulation of scytophycin accumulation in cultures of Scytonema ocellatum. I. Physical factors

Scytonema ocellatum (Cyanobacteria or Cyanophyta) produces macrolide antibiotics of the scytophycin family that are antifungal, cytostatic agents and act by disrupting actin microfilaments. Scytophycin accumulation paralleled vegetative growth. Tolytoxin continued to accumulate throughout the growth cycle, whereas 6-hydroxy-7-O-methylscytophycin E (HMSE) and 19-O-demethylscytophycin C (DMSC) reached plateau levels prior to cessation of growth, suggesting a logical biosynthetic pathway of DMSC → ? → HMSE → tolytoxin. A rapid decrease in scytophycin content observed in newly inoculated cultures suggests that the scytophycins are continuously metabolized. The optimal temperature for production was 25°C. Continuous illumination at an intensity of at least 25 μml photons m^?2 s^?1 was required for maximum yield. Growth and metabolite production were optimal in the pH range of 8.0 to 8.5.     

ANTIVIRAL ACTIVITY OF CULTURED BLUE-GREEN ALGAE (CYANOPHYTA)1

Lipophilic and hydrophilic extracts from approximately 600 strains of cultured cyanophytes, representing some 300 species, were examined for antiviral activity against three pathogenic viruses. Approximately 10% of the cultures produced substances that caused significant reduction in cytopathic effect normally associated with viral infection. The screening program identified the order Chroococcales as commonly producing antiviral agents.