4,6,8,10,16-penta- and 4,6,8,10,16,18-hexamethyldocosanes from the cane beetle Antitrogus parvulus - Cuticular hydrocarbons with unprecedented structure and stereochemistry

[GRAPHICS] The major cuticular hydrocarbons from the cane beetle species Antitrogus parvulus were deduced to be 4,6,8,10,16,18-hexa- and 4,6,8,10,16-pentamethyldocosanes 2 and 3, respectively. Isomers of 2,4,6,8-tetramethylundecanal 27, 36, and 37, derived from 2,4,6-trimethylphenol, were coupled with the phosphoranes 28 and 29 to furnish alkenes and, by reduction, diastereomers of 2 and 3. Chromatographic and spectroscopic comparisons confirmed 2 as either 6a or 6b and 3 as either 34a or 34b.

Novel sesquiterpenes from the fungus lactarius piperatus

Four novel sesquiterpenes, namely 7alpha,8beta,13-trihydroxy-5,13-marasmanolide (2), isoplorantinone (5), 4,8,14-trihydroxyilludala-2,6,8-triene (6), and 8-hydroxy-8,9-secolactara-1,6-dien-5,13-olide (10), together with six known ones, 7alpha,8beta-dihydroxy-5,13-marasmanolide (1), 7alpha,8alpha-dihydroxy-5,13-marasmanolide (3), isolactarorufin (4), blennin A (7), blennin D (8), and lactarorufin (9), were isolated from the ethanolic extract of Lactarius piperatus. The structures of these sesquiterpenes, representing diversified structural types, were determined mainly by spectroscopic methods, especially 2D-NMR techniques. The structure of 6 was further confirmed by a single-crystal X-ray-diffraction determination.

Characterisation of alkaloids from some Australian Stephania (Menispermaceae) species

Chemical investigations of some Stephania species native to Australia and reportedly employed by Aboriginal people as therapeutic agents. are described. The alkaloids from the forest vines Stephania bancroftii F.M. Bailey and S. aculeata F.M. Bailey (Menispermaceae) have been isolated and characterised. The major alkaloids in the tuber of the former species are (-)-tetra-hydropalmatine and (-)-stephanine, whereas these are minor components in the leaves, from which a C-7 hydroxylated aporphine has been identified. The major tuber alkaloids in S. aculcata are (+)-laudanidine, and the morphinoid, (-)-amurine, whose absolute stereochemistry has been established by X-ray structural analysis of the methiodide derivative. No significant levels of alkaloids were detected in S. japonica. Complete and unambiguous H-1 and C-13 NMR data are presented for these alkaloids. (C) 2003 Elsevier Ltd. All rights reserved.

Development of lipid-core-peptide (LCP) based vaccines for the prevention of the group A streptococcal (GAS) infection

Traditional vaccines consisting of whole attenuated micro-organisms. or microbial components administered with adjuvant, have been demonstrated as one of the most cost-effective and successful public health interventions. Their use in large scale immunisation programs has lead to the eradication of smallpox, reduced morbidity and mortality from many once common diseases, and reduced strain on health services. However, problems associated with these vaccines including risk of infection. adverse effects, and the requirement for refrigerated transport and storage have led to the investigation of alternative vaccine technologies. Peptide vaccines, consisting of either whole proteins or individual peptide epitopes, have attracted much interest, as they may be synthesised to high purity and induce highly specific immune responses. However, problems including difficulties stimulating long lasting immunity. and population MHC diversity necessitating multiepitopic vaccines and/or HLA tissue typing of patients complicate their development. Furthermore, toxic adjuvants are necessary to render them immunogenic. and as such non-toxic human-compatible adjuvants need to be developed. Lipidation has been demonstrated as a human compatible adjuvant for peptide vaccines. The lipid-core-peptide (LCP) system. incorporating lipid adjuvant, carrier, and peptide epitopes, exhibits promise as a lipid-based peptide vaccine adjuvant. The studies reviewed herein investigate the use of the LCP system for developing vaccines to protect against group A streptococcal (GAS) infection. The studies demonstrate that LCP-based GAS vaccines are capable of inducing high-titres of antigen specific IgG antibodies. Furthermore. mice immunised with an LCP-based GAS vaccine were protected against challenge with 8830 strain GAS.

Transdermal delivery of a tetrapeptide: Evaluation of passive diffusion

Skin penetration of the tetrapeptide Ac-Ala-Ala-Pro-Val-NH2 was assessed. This peptide sequence fits the P-P-1 subsites of elastase and inhibits human neutrophil elastase competitively. Consequently this peptide may be therapeutically useful in a variety of inflammatory disorders, including psoriasis. in which elevated levels of human neutrophil elastase have been reported. Peptide penetration was assessed across whole human skin, whole skin with the stratum corneum removed by tape stripping and epidermis, which had been removed from the dermis by heat separation. The influence of 75% aqueous ethanol as a potential penetration enhancer of the tetrapeptide across epidermis was also assessed. The tetrapeptide did not penetrate whole human skin or epidermis, even under the influence of 75% aqueous ethanol. However, when the stratum corneum was removed tetrapeptide flux of 73.39 mug cm(-2) h(-1) was achieved. The study demonstrates that the stratum corneum is the main barrier to tetrapeptide skin penetration and must be overcome if therapeutically relevant amounts of tetrapeptide are to be delivered to the skin.

Probing the pore wall structure of nanoporous carbons using adsorption

Hitherto, adsorption has been traditionally used to study only the porous structure in disordered materials, while the structure of the solid phase skeleton has been probed by crystallographic methods such as X-ray diffraction. Here we show that for carbons density functional theory, suitably adapted to consider heterogeneity of the pore walls, can be reliably used to probe features of the solid structure hitherto accessibly only approximately even by crystallographic methods. We investigate a range of carbons and determine pore wall thickness distributions using argon adsorption, with results corroborated by X-ray diffraction.

Nematocidal thiocyanatins from a southern Australian marine sponge Oceanapia sp.

Investigations of a southern Australian marine sponge, Oceanapia sp., have yielded two new methyl branched bisthiocyanates, thiocyanatins D-1 (3a) and D-2 (3b), along with two new thiocarbamate thiocyanates, thiocyanatins E-l (4a) and E-2 (4b). The new thiocyanatins belong to a rare class of bioactive marine metabolite previously only represented by thiocyanatins A-C (1, 2a/b). Structures were assigned on the basis of detailed spectroscopic analysis, with comparisons to the known bisthiocyanate thiocyanatin A (1) and synthetic model compounds (5-7). The thiocyanatins exhibit potent nematocidal activity, and preliminary structure-activity relationship investigations have confirmed key characteristics of the thiocyanatin pharmacophore.

Blanchaquinone: A new anthraquinone from an Australian Streptomyces sp.

Chemical analysis of an Australian Streptomyces species yielded a range of known anthracyclines and biosynthetically related metabolites, including daunomycin (1), E-rhodomycinone (2), 11-hydroxyauramycinone (3), 11-hydroxysulfurmycinone (4), aklavinone (5), bisanhydro-gamma-rhodomycinone (6), and the anthraquinone 7, as well as the hitherto unreported blanchaquinone (8). The structure assigned to 8 was secured by detailed spectroscopic analysis and correlation to known analogues, such as the anthraquinone 7. This account also represents the first natural occurrence of 3, 4, and 7 and the first spectroscopic characterization of 11-hydroxysulfurmycinone (4).

Rugulotrosins A and B: Two new antibacterial metabolites from an Australian isolate of a penicillium sp.

Two new antibacterial agents, rugulotrosin A (1) and B (2), were obtained from cultures of a Penicillium sp. isolated from soil samples acquired near Sussex Inlet, New South Wales, Australia. Rugulotrosin A (1) is a chiral symmetric dimer, and its relative stereostructure was determined by spectroscopic and X-ray crystallographic analysis. Rugulotrosin B (2) is a chiral asymmetric dimer isomeric with 1. Its structure was determined by spectroscopic analysis with comparison to the co-metabolite 1 and previously reported fungal metabolites. Both rugulotrosins A and B displayed significant antibacterial activity against Bacillus subtilis, while rugulotrosin A was also strongly active against Enterococcus faecalis and B. cereus.

Wurst: a protein threading server with a structural scoring function, sequence profiles and optimized substitution matrices

Wurst is a protein threading program with an emphasis on high quality sequence to structure alignments (http://www.zbh.uni-hamburg.de/wurst). Submitted sequences are aligned to each of about 3000 templates with a conventional dynamic programming algorithm, but using a score function with sophisticated structure and sequence terms. The structure terms are a log-odds probability of sequence to structure fragment compatibility, obtained from a Bayesian classification procedure. A simplex optimization was used to optimize the sequence-based terms for the goal of alignment and model quality and to balance the sequence and structural contributions against each other. Both sequence and structural terms operate with sequence profiles.

Fluctuations and single molecules

The fluorescence of single molecules coupled to a thermal bath is studied both experimentally and theoretically. The effect of different fluctuations on the coherence properties of resonance fluorescence is considered first. Coherence is measured in an interference experiment where a single molecule is used as a light source. A standard approach based on the optical Bloch equations apparently provides quite an accurate description of the interference experiment. Systems with long correlation times (where spectra are time dependent on any timescale) are considered next. It is shown that intensity-time-frequency correlation spectroscopy, which provides both high signal-to-noise ratio and high time resolution, is very suitable for such a case. The Bloch equations are further tested in an experiment where the shape of an excitation spectral line of a single molecule is accurately measured over six orders of magnitude of the exciting laser power. Significant deviations from the predictions of the Bloch equations are found. The role of critical parameters-the correlation time of the bath, the Rabi oscillation period, and the coupling constant between the bath and the molecule-is discussed. The paper also includes a short general introduction to the methodology of single-molecule studies.

Structure of the N-terminal domain of Escherichia coli glutamine synthetase adenylyltransferase

We report the crystal structure of the N-terminal domain of Escherichia coli adenylyltransferase that catalyzes the reversible nucleotidylation of glutamine synthetase (GS), a key enzyme in nitrogen assimilation. This domain (AT-N440) catalyzes the deadenylylation and subsequent activation of GS. The structure has been divided into three subdomains, two of which bear some similarity to kanamycin nucleotidyltransferase (KNT). However, the orientation of the two domains in AT-N440 differs from that in KNT. The active site of AT-N440 has been identified on the basis of structural comparisons with KNT, DNA polymerase beta, and polyadenylate polymerase. AT-N440 has a cluster of metal binding residues that are conserved in polbeta-like nucleotidyl transferases. The location of residues conserved in all ATase sequences was found to cluster around the active site. Many of these residues are very likely to play a role in catalysis, substrate binding, or effector binding.

Prediction of high-pressure adsorption equilibrium of supercritical gases using density functional theory

In this paper, we present the results of the prediction of the high-pressure adsorption equilibrium of supercritical. gases (Ar, N-2, CH4, and CO2) on various activated carbons (BPL, PCB, and Norit R1 extra) at various temperatures using a density-functional-theory-based finite wall thickness (FWT) model. Pore size distribution results of the carbons are taken from our recent previous work 1,2 using this approach for characterization. To validate the model, isotherms calculated from the density functional theory (DFT) approach are comprehensively verified against those determined by grand canonical Monte Carlo (GCMC) simulation, before the theoretical adsorption isotherms of these investigated carbons calculated by the model are compared with the experimental adsorption measurements of the carbons. We illustrate the accuracy and consistency of the FWT model for the prediction of adsorption isotherms of the all investigated gases. The pore network connectivity problem occurring in the examined carbons is also discussed, and on the basis of the success of the predictions assuming a similar pore size distribution for accessible and inaccessible regions, it is suggested that this is largely related to the disordered nature of the carbon.