Structure–antimicrobial activity of some natural isocoumarins and their analogues

Three naturally occurring isocoumarins (paepalantine, paepalantine 9-O-beta-D-glucopyranoside and paepalantine 9-O-beta-D-allopyranosyl(1 --> 6) glucopyranoside) and two semi-synthetic analogues, 9,10-acylated compound and 9-OH-10-methylated compound, structurally similar to paepalantine, were evaluated for antimicrobial activity using a spectrophotometric microdilution technique. The paepalantine was active against S. aureus, S. epidermidis, and E. faecalis while the other four compounds proved ineffective against all microorganisms tested at concentrations of 500 microg/ml. Variations in phenolic substitution at OH-9 and/or OH-10 in the paepalantine molecule resulted in compounds without antimicrobial activity. A combination of structural features, two phenolic groups as cathecolic system, forms an oxygenated system arrangement that may reflect the potentially antimicrobial properties of paepalantine.     

Contribution of unusual Arginine-Arginine short-range interactions to stabilization and recognition in proteins

Although the majority of the ion pairs found in proteins consists of two charges of opposite sign, the observation of some unusual arrangements of two arginines led us to a search of such occurrences in the Brookhaven Protein Data Bank. We have found 41 Arginine-Arginine interactions with a C...C distance less than 5 å. Computer graphics analysis of these structures shows that most of the Arg-Arg pairs are found in the vicinity of the surface of the proteins, in an easily hydrated region. In order to determine which factors could stabilize such arrangements of species of similar charge, we have carried out AM1 semi-empirical calculations on a model of two guanidinium ions surrounded by several water molecules. The results show the existence of stable clusters with six or more water molecules, with distances between C atoms around 3 å. The bridging role of the water molecules is an important structural and energetic feature and we find bridges of two and three molecules between the guanidinium ions. These results are in good agreement with the structures found in our search of the experimental data. Enhancement of the electrostatic potential around these clusters, when compared to one of the guanidinium ions alone, is also demonstrated.     

Expression of {beta}-galactoside {alpha}2,6-sialyltransferase does not alter the susceptibility of human colon cancer cells to NK-mediated cell lysis

The extent of processing of N-linked oligosaccharides and thesialylation of the target cell membranes has been positivelycorrelated with resistance to lysis mediated by NK cells, buta conclusive evidence has never been reached. Colon cancer tissuesexpress an increased activity of ß-ga-lactoside     

Differential effects of manganese ions on Blastocladiella emersonii adenylate cyclase.

Adenylate cyclase (ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1) activity in Blastocladiella emersonii is associated with particulate subcellar fractions. Solubilization after treatment with detergent suggests its localization in a membrane fraction of the zoospore homogenate. The enzyme specifically requires Mn2+ for activity and is not stimulated by NaF. The kinetic characteristics of substrate utilization by B. emersonii adenylate cyclase were investigated with various concentrations of ATP and Mn2+, and in the presence of inhibitors. Plots of enzyme activity versus the actual concentration of the MnATP2- complex give sigmoid curves. An excess of Mn2+ activates the enzyme at low concentrations of substrate and leads to a modification of the enzyme kinetics. The nucleotides 5'-AMP and GTP were shown to be competitive inhibitors of the enzyme. In addition, kinetic data, obtained under conditions in which an inhibitor (ATP) is added in constant proportion to the variable substrate (MnATP2-) concentration, produced reciprocal plots that were linear and intersecting to the right of the ordinate, and secondary replots that were hyperbolic. These kinetic patterns support a model in which: MnATP2- is the substrate; free Mn2+ is an activator at low substrate concentrations, but an inhibitor at high substrate concentrations; and free ATP is not an efficient inhibiyor (Ki greater than 1.10(-4) M).     

Common and rare species respond to similar niche processes in macroinvertebrate metacommunities

Ecologists have long investigated why communities are composed of a few common species and many rare species. Most studies relate rarity to either niche differentiation among species or spatial processes. There is a parallel between these processes and the processes proposed to explain the structure of metacommunities. Based on a metacommunity perspective and on data on stream macroinvertebrates from different regions of Brazil, we answer two questions. 1) Are sets of common and rare species affected by similar niche and spatial processes? 2) How does the community composition of common and of rare species differ? The main hypothesis we test is that common species are mainly affected by environmental factors, whereas rare species are mostly influenced by dispersal limitation. We used variation partitioning to determine the proportion of variation explained by the environment and space in common and rare species matrices. Contrary to our expectations, evidence supported the idea that both common and rare species are affected mainly by environmental factors, even after controlling for the differing information content between common and rare species matrices. Moreover, the abundance of some common species is also a good predictor of variation in rare species matrices. Niche differences are unlikely to be the sole cause of patterns of rarity in these metacommunities. We suggest that sets of common and rare species react to similar major environmental gradients and that rare species also respond to processes that operate at a more fine‐grained spatial scale, particularly biotic interactions. We extend the view that species sorting is the dominant process structuring metacommunities and argue that future studies focusing on rarity would benefit from a metacommunity perspective.     

Serendipitous syntheses of Rh(H)2Cl(PRPh2)3 complexes, and their crystal structures, where R = Me, Cy (cyclohexyl)

Reactions of RhCl(cod)(THP) (cod = 1,5-cyclooctadiene; THP = P(CH₂OH)₃) with PMePh₂ or PCyPh₂ (Cy = cyclohexyl) in acetone/MeOH solution under H₂ surprisingly form the complexes cis, mer-Rh(H)₂Cl(PRPh₂)₃ (R = Me or Cy); both complexes are characterized by crystallography (the first structures in which the hydride ligands of such dihydrido-chloro-trisphosphine complexes have been located), and by detailed ¹H and ³¹P NMR spectroscopy. The key role of the THP in the observed chemistry is discussed.     

Isolation and purification of a lethal scorpion toxin with neuromuscular blocking activity

Toxin-L a lethal neuromuscular blocking agent was isolated from the venom of the scorpion, Lychas laevifrons (Pocock), by the CM-cellulose ion-exchange chromatography. It was a homogenous, thermolabile and low molecular weight protein. The toxin produced irreversible blockade of indirect stimulation induced twitch responses on innervated rat phrenic nerve-diaphragm and chick biventer cervicis preparation. The toxin did not produce any contractile response on toad rectus abdominis muscle preparation. On chronically denervated rat diaphragm, the toxin failed to alter the responses induced by direct stimulation, exogenous acetylcholine, potassium chloride and caffeine. Acetylcholine and carbachol induced contractions on isolated chick biventer cervicis remained unaltered by the toxin. Neostigmine failed to alter toxin induced neuromuscular blockade on innervated rat diaphragm. The toxin released a significant amount of acetylcholine from innervated rat diaphragm. It may be concluded that the toxin acts presynaptically through the release of acetylcholine, thereby producing neuromuscular blockade.