Specific antimicrobial and hemolytic activities of 18-residue peptides derived from the amino terminal region of the toxin pardaxin

Peptides are part of the host defense system against bacteriaand fungi in species right across the evolutionary scale. However,endogenous antibacterial peptides are often composed of 25 residuesor more and, therefore, are not ideal for therapeutic use. Henceit is of considerable interest to design and engineer shortpeptides having antimicrobial activity. Peptides composed of18 amino acids, derived from the N-terminal region of the 33-residuetoxiri pardaxin (PX), GFFALIPKDSSPLFKTLLSAVGSALSSSGEQE, weresynthesized and examined for biological activities. Peptidecorresponding to the 1-18 stretch of PX exhibited antimicrobialactivity only against Escherichia coli and not against Gram-positivemicroorganisms. The peptide also did not possess hemolytic activity.Replacement of P7 by A resulted in a peptide possessing bothantibacterial and hemolytic activity. Substitution of both Kresidues by Q in the 'A' analog resulted in a peptide havingpeptides and investigation of their model membrane permeabilizingactivities indicated that selective activity can be explainedby their biophysical properties. Hence, by a rational designapproach based on biophysical principles, it should be possibleto generate short peptides having specific biological activity.     

On the possibilities of immobilization and utilization of some cellulase enzymes

Cellulase enzymes produced by the microorganisms Aspergillus niger and Trichoderma viride have been immobilized on Ponilex type ion exchangers, both by ionic and by covalent bonding. Immobilization efficiency has been determined for enzyme preparations obtained, by their activity, as well as by that of the resulted effluent, on using as substrate carboxymethyl cellulose, cellobiose, and filter paper. The catalytic activity of the immobilized products has been tested against solutions of carboxymethyl cellulose and a series of hemicellulose containing alkaline extracts resulted from the alkaline pretreatments of some vegetal materials. The presence of polyphenol compounds in the latter ones determines a series of peculiarities in the behavior of the enzyme preparations, such as the transformation of the hydrolysis products and reduction of thecatalytic activity of the enzyme, after a certain period of reaction.     

Synthesis and Evaluation of a Series of Bis(pentylpyridinium) Compounds as Antifungal Agents

A series of bis(4‐pentylpyridinium) compounds with a variety of spacers between the pyridinium headgroups was synthesised, and the antifungal activity of these compounds was investigated. Lengthening the alkyl spacer between the pentylpyridinium headgroups from 12 to 16 methylene units resulted in increased antifungal activity against C. neoformans and C. albicans, but also resulted in increased hemolytic activity and cytotoxicity against mammalian cells. However, inclusion of an ortho‐substituted benzene ring in the centre of the alkyl spacer resulted in decreased cytotoxicity and hemolytic activity, while maintaining antifungal potency. Replacement of the alkyl and aromatic‐containing spacers by more hydrophilic ethylene glycol groups resulted in a loss of antifungal activity. Some of the compounds inhibited fungal PLB1 activity, but the low correlation of this inhibition with antifungal potency indicates PLB1 inhibition is unlikely to be the predominant mode of antifungal action of this class of compounds, with preliminary studies suggesting they may act via disruption of fungal mitochondrial function.     

Optimisation of the anti-Trypanosoma brucei activity of the opioid agonist U50488

Screening of the Sigma-Aldrich Library of Pharmacologically Active Compounds (LOPAC) against cultured Trypanosoma brucei, the causative agent of African sleeping sickness, resulted in the identification of a number of compounds with selective antiproliferative activity over mammalian cells. These included (+)-(1R,2R)-U50488, a weak opioid agonist with an EC(50) value of 59 nM as determined in our T. brucei in vitro assay reported previously. This paper describes the modification of key structural elements of U50488 to investigate structure-activity relationships (SAR) and to optimise the antiproliferative activity and pharmacokinetic properties of this compound.     

Distribution of the phosphatidate phosphohydrolase activity in the lamellar body and lysosomal fractions of lung tissue

Phosphatidate phosphohydrolase (PAPase) activity was measured in lamellar bodies purified from porcine lung tissue. After repeated freeze-thawing, only a negligible amount of PAPase activity was released into the soluble fractions, whereas there was release of 2 lysosomal marker enzyme activities, glucosaminidase and β-galactosidase into the soluble fraction. In addition, a lysosomal-enriched fraction was prepared from adult rat lung tissue by prior treatment of the rats with Triton WR 1339. Treatment with Triton WR 1339 resulted in the significant shift of the activities of the lysosomal marker enzymes, glucosaminidase and β-galactosidase, to less dense subcellular fractions. The highest specific activity of PAPase was found in a subcellular fraction which had a density that was intermediate between that of the mitochondrial and microsomal fractions and the distribution of PAPase activity was not affected by the prior treatment of the rats with Triton WR 1339.     

Influence of the Alkali Promoter on the Activity and Stability of Transition Metal (Cu, Co, Fe) Based Structured Catalysts for the Simultaneous Removal of Soot and NOx

Structured catalysts prepared by means of coating cordierite monoliths with alumina-based suspensions containing transition metals such as Cu, Co and Fe and alkali/alkali-earth promoters such as K and Ba. Textural and structural features of these catalysts were analyzed by means of N₂ adsorption and SEM. Their activity in the simultaneous removal of soot and NO_x was assayed in a lab-scale installation, using a carbon black as diesel surrogate. Catalysts exhibited significant activity in deNO_x and soot oxidation. K and Ba enhanced both NO_x adsorption and soot–catalyst contact. However Ba contributed to a greater extent to the adsorption of N-species, which moreover presented higher thermal stability than on K-catalysts, and K showed higher mobility than Ba. Thus, Ba-containing catalysts showed increased activity towards NO_x reduction but shifted to higher temperatures in comparison to K-catalysts, which on the other hand resulted more active towards soot oxidation than Ba-ones. Fe-based catalyst turned out to be less active both in soot oxidation and NO_x reduction than Co and Cu-based ones. Intensive calcination of the catalysts at 800 °C for 5 h resulted in substantial loss of K and Ba. Loss of promoter depends, however, on the metal contained in the catalyst. In this sense Fe-containing catalysts showed higher stability. Calcination has a substantial effect on catalytic activity. Catalyst significantly lost their NO_x adsorption capacity and showed similar activity than a catalyst prepared in absence of promoter, pointing to a substantial change in reaction mechanism and reaction predominantly occurring on metallic sites upon the loss of alkali/alkali-earth compound.     

Modulation of proteasome machinery by natural and synthetic analogues of the marine bioactive compound petrosaspongiolide M

Natural or synthetic? Several petrosaspongiolide M natural and synthetic analogues have been tested as proteasome inhibitors and apoptosis modulators. The natural petrosaspongiolide M congeners gave a consistent decrease in activity. Among the synthetic analogues, the introduction of the benzothiophene ring resulted in a bioequivalent alternative of the petrosaspongiolide M terpenoid system.     

Potassium-doped sodalite: A tectoaluminosilicate for the catalytic material towards continuous combustion of carbonaceous matters

A novel approach has been proposed for stabilization of potassium in combustion of carbonaceous soot matters emitted from diesel engine vehicles. Sodalite, a clathrate aluminosilicate zeolite, is employed as a support for holding catalytically active potassium species. This approach resulted in a high-catalytic activity and the activity is further enhanced after hydrothermal treatment at 800 °C. Such kinds of tectoaluminosilicate hold potassium strongly and possess high stability against high temperatures and alkaline conditions induced by hydrated potassium ions under practical driving conditions.     

The carboxyl-terminal region of human interferon {gamma} is important for biological activity: mutagenic and NMR analysis

Deletion of nine amino acids from the carboxyl terminus of humanIFN (residues 138–146; LFRGRRASQ) resulted in a 7-foldincrease in specific antiviral activity. Similar increases inreceptor binding affinity were seen. Deletion of residues 136and 137 (QM) had little additional effect, but removal of Ser135resulted in a sharp drop in antiviral activity. Further removalof residues 133 and 134 (KR) lowered antiviral activity to 1%of the peak value. Comparison of the proton NMR spectra of selecteddeletions down to residue 132 showed that there was no significantchange in the core protein structure. Deletions down to residue125 had the same antiviral activity as those to 132, but changescould now be seen in the aromatic proton NMR spectrum of thisshorter derivative. Substitution of the homologous murine sequencebetween residues 124 and 130 (human SPAAKTG; murine LPESSLR)resulted in only a small decrease in antiviral activity, furthersuggesting that the precise sequence in this region was notcritical for activity. Ser135 was substituted with a numberof other amino acids with little or no change in activity. Theimportance of the residues between 131 and 134 for biologicalactivity was corroborated by mutagenesis, although some substitutionsin this region were tolerated.     

Defining the Role of Flavonoid Structure on Cottonseed Oil Stabilization: Study of A- and C-Ring Substitution

Structure—activity relationships of flavonoids against cottonseed oil oxidation are the objective of this work, which focuses on the contribution of C-ring and 5,7-di-OH A-ring. Flavonoids with a catecholic B-ring, namely quercetin, fisetin, luteolin, taxifolin, (+)-catechin and eriodictyol were added in increasing concentrations to cottonseed oil and the induced decrease in the rate constant of peroxide formation (k) and peroxide values (PV) were determined. The flavonoid depletion was monitored during the autoxidation with high-performance liquid chromatography-diode array detector (HPLC-DAD) analysis. The fully substituted C-ring was established as the most significant element for maximal antioxidant activity; quercetin even decreased k by 86% in comparison with the control and presented the highest decrease of PV per mmole of antioxidant. Flavonoids missing the 2,3-double bond or the 3-OH (taxifolin, luteolin) resulted in a smaller decrease of k, and the lack of both of the above structural elements (eriodictyol) resulted in the smallest decrease. Lack of the 4-carbonyl in the C-ring had the least negative effect on antioxidant activity since (+)-catechin presented the strongest protection after quercetin and fisetin. The activity of the latter flavonoid proved that A-ring hydroxyls, despite the unfavorable m-configuration, participate in the stabilization of the lipid substrate, although their significance was secondary.     

Characterization of the amino acids essential for the photo- and radioprotective effects of a Bowman-Birk protease inhibitor-derived nonapeptide

The Bowman–Birk protease inhibitor has been reported toexert photo- and radioprotective activity. This effect was assignedto a cyclic nonapeptide sequence which is known to contain theamino acids responsible for the anti-chymotryptic activity ofthe BBI. The present study indicated that linearization of thenonapeptide resulted in a significant loss of anti-proteolyticactivity, whereas the photo- and radioprotective capacity persisted.Substitution of the amino acids Leu or Ser of the nonapeptide,essential for the anti-proteolytic activity, with differentamino acids, indicated that rather the hydrophobic featuresof the amino acids in this position than charge are criticalto retain the photo- and radioprotective effect. These resultssuggest the existence of a bifunctional peptide sequence withanti-proteolytic and photo-/radioprotective capacity. However,the lack of correlation between the photo-/radioprotective activityand the anti-proteolytic activity within the peptides generatedby modification of the linear nonapeptide argues for the existenceof two closely colocalized domains within the nonapeptide responsiblefor photo-/radioprotection and protease inhibition.     

Crosslinked TS-1 as stable catalyst for the Beckmann rearrangement of cyclohexanone oxime

Crosslinked TS-1 zeolite materials have been studied in the gas phase Beckmann rearrangement reaction of cyclohexanone oxime to ε-caprolactam. Crosslinking of the zeolite particles resulted in the formation of an additional mesoporosity leading to increased activity in the Beckmann rearrangement reaction. The increased activity can be correlated with the newly created mesopore surface. Possibly more important, together with increased catalytic activity of the materials, the deactivation behavior of the catalysts is very significantly improved.     

硅源对Bi-MSU-4结构及催化性能的影响

分别以正硅酸乙酯、硅溶胶、硅酸钠和硅胶H为硅源,聚氧乙烯失水山梨醇软脂酸单酯（Tween-40）为模板剂,硝酸铋为铋源,合成出一种含铋的介孔分子筛Bi-MSU-4。采用X射线衍射（XRD）、紫外-可见光谱（UV-vis）和扫描电镜（SEM）对样品进行表征。并将所合成的Bi-MSU-4用于苯乙烯选择性反应中考察其催化活性。结果表明,硅源对Bi-MSU-4的结构和催化性能产生较大的影响。以正硅酸乙酯、硅酸钠为硅源,由于其水解速率缓慢,有利于分子筛的合成,所制得的样品相对结晶度和催化活性度较高;硅溶胶水解－聚合速率过快不能与模板剂完全作用,所制得的样品规整性较差,结晶度和苯乙烯的转化率都有所下降;酸性条件下不利于硅胶H的水解,反应体系中仍有硅胶H微粒的存在,从而大大影响其产物的结晶度和催化性能。     

Structure Sensitivity of Nano-structured CdS/SBA-15 Containing Au and Pt Co-catalysts for the Photocatalytic Splitting of Water

Photocatalysts containing nanocrystallites of cadmium sulphide dispersed in the channels of mesoporous silicate SBA-15 exhibited enhanced activity for visible-light mediated splitting of water, as compared to bulk CdS. Whereas the incorporation of 1 wt.% Pt co-catalyst in CdS/SBA-15 led to a substantial increase in H₂ yield, Au at similar loading resulted in marginally decreased activity. The results indicate that the photocatalytic activity of CdS crystallites is structure sensitive. Similarly, the role of a noble metal may be associated with the particle size dependent micro-structural features, rather than its electronic properties such as the work function or the heat of adsorption of reactant or product molecules.     

Influence of lattice integrity and phase composition on the photocatalytic hydrogen production efficiency of ZnS nanomaterials

Ambient S annealing was adopted to regulate the crystallinity of a ZnS microsphere, which resulted in a significant improvement in the photocatalytic hydrogen production activity (PHPA). Moreover, with S ambient treatment, wurtzite ZnS showed better PHPA than sphalerite ZnS, possibly because the inter-polar electric field of the wurtzite phase could promote the separation of photo-excited electron-hole pairs.     

Structure-Activity Relationships for 5′′ Modifications of 4,5-Aminoglycoside Antibiotics

Modification at the 5’’-position of 4,5-disubstituted aminoglycoside antibiotics (AGAs) to circumvent inactivation by aminoglycoside modifying enzymes (AMEs) is well known. Such modifications, however, unpredictably impact activity and affect target selectivity thereby hindering drug development. A survey of 5’’-modifications of the 4,5-AGAs and the related 5-O-furanosyl apramycin derivatives is presented. In the neomycin and the apralog series, all modifications were well-tolerated, but other 4,5-AGAs require a hydrogen bonding group at the 5’’-position for maintenance of antibacterial activity. The 5’’-amino modification resulted in parent-like activity, but reduced selectivity against the human cytosolic decoding A site rendering this modification unfavorable in paromomycin, propylamycin, and ribostamycin. Installation of a 5’’-formamido group and, to a lesser degree, a 5’’-ureido group resulted in parent-like activity without loss of selectivity. These lessons will aid the design of next-generation AGAs capable of circumventing AME action while maintaining high antibacterial activity and target selectivity.     

Discovery of the Class I Antimicrobial Lasso Peptide Arcumycin

Lasso peptides are a structurally diverse superfamily of conformationally constrained peptide natural products, of which a subset exhibits broad antimicrobial activity. Although advances in bioinformatics have increased our knowledge of strains harboring the biosynthetic machinery for lasso peptide production, relating peptide sequence to bioactivity remains a continuous challenge. To this end, genome mining investigation of Actinobacteria-produced antimicrobial lasso peptides was performed to correlate predicted structure with antibiotic activity. Bioinformatic evaluation revealed eight putative novel class I lasso peptide sequences. Fermentation of one of these hits, Streptomyces NRRL F-5639, resulted in the production of a novel class I lasso peptide, arcumycin. Arcumycin exhibited antibiotic activity against Gram-positive bacteria including Bacillus subtilis (4 μg/mL), Staphylococcus aureus (8 μg/mL), and Micrococcus luteus (8 μg/mL). Arcumycin treatment of B. subtilis liaI-β-gal promoter fusion reporter strain resulted in upregulation of the liaRS system by the promoter liaI, indicating arcumycin interferes with lipid II biosynthesis. Cumulatively, the results illustrate the relationship between phylogenetically related lasso peptides and their bioactivity as validated through the isolation, structural determination, and evaluation of bioactivity of the novel class I antimicrobial lasso peptide arcumycin.     

Copolymerization of carbon dioxide and propylene oxide with zinc glutarate as catalyst in the presence of compounds containing active hydrogen

To enhance the catalytic copolymerization of CO₂ and propylene oxide catalyzed by zinc glutarate, the influence of trace of water, ethanol, and propanal on the catalytic activity, the resulted copolymer structure, and the molecular weight and molecular weight distribution of the copolymer were investigated extensively. The experimental results showed that the catalytic activity decreased remarkably in the presence of either trace of ethanol or water, but increased in the presence of trace of propanal. Both ¹H‐NMR and ¹³C‐NMR spectra suggested that the content of carbonate linkages of resulted copolymer was not effected obviously in the presence of above‐mentioned impurities, giving completely alternating poly(propylene carbonate) (PPC). GPC results indicated that these impurities reduced the molecular weights but broadened the molecular weight distributions of resulted copolymers. Finally, the byproduct contents including both propylene carbonate determined by GC and polyether increased with the increase of three impurity concentrations. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 2007     

Modification of the preparation procedure for increasing the hydrodesulfurisation activity of the CoMo/γ-alumina catalysts

In this work we have examined whether the re-impregnation of CoMo/γ-alumina catalysts or the replacement of the conventional non-dry impregnation step by “equilibrium deposition filtration” (EDF) may be used for improving their surface characteristics and thus their catalytic activity.

Two samples were prepared. In the first sample (EDF) the molybdenum species were mounted by “equilibrium deposition filtration” whereas in the second sample these species were mounted by non-dry impregnation (NDI). In both cases the Co was deposited on the calcined Mo/γ-Al₂O₃ precursor solid by simple dry impregnation. An aliquot of each sample was impregnated again with an amount of pure water equal to its pore volume and then it underwent drying and calcination.

The catalysts prepared were characterized using N₂ adsorption measurements (BET), UV–vis diffuse reflectance spectroscopy (DRS), laser Raman spectroscopy (LRS) and NO chemisorption. The hydrodesulfurization (HDS) activities over the catalysts studied were determined using a continuous-flow tubular fixed-bed microreactor operating in a differential mode at atmospheric pressure.

It was confirmed that the replacement of the conventional impregnation by equilibrium deposition filtration results to catalysts with relatively high active surface and high portion of the well-dispersed octahedral cobalt and thus, to catalysts with 30% higher HDS activity. The re-impregnation resulted to partial dissolution and re-dispersion of the Mo and Co supported oxidic phases. Concerning the NDI catalyst re-impregnation resulted to an increase of the active surface and of the portion of the well-dispersed octahedral cobalt and thus to 25% higher catalytic activity. The opposite effects were observed for the EDF catalyst which exhibited almost 7% lower activity after re-impregnation.     

Improving the Therapeutic Index of Smp24, a Venom-Derived Antimicrobial Peptide: Increased Activity against Gram-Negative Bacteria

Antimicrobial peptides (AMPs) are naturally occurring compounds which possess a rapid killing mechanism and low resistance potential. Consequently, they are being viewed as potential alternatives to traditional antibiotics. One of the major factors limiting further development of AMPs is off-target toxicity. Enhancements to antimicrobial peptides which can maximise antimicrobial activity whilst reducing mammalian cytotoxicity would make these peptides more attractive as future pharmaceuticals. We have previously characterised Smp24, an AMP derived from the venom of the scorpion Scorpio maurus palmatus. This study sought to better understand the relationship between the structure, function and bacterial selectivity of this peptide by performing single amino acid substitutions. The antimicrobial, haemolytic and cytotoxic activity of modified Smp24 peptides was determined. The results of these investigations were compared with the activity of native Smp24 to determine which modifications produced enhanced therapeutic indices. The structure–function relationship of Smp24 was investigated by performing N-terminal, mid-chain and C-terminal amino acid substitutions and determining the effect that they had on the antimicrobial and cytotoxic activity of the peptide. Increased charge at the N-, mid- and C-termini of the peptide resulted in increased antimicrobial activity. Increased hydrophobicity at the N-terminus resulted in reduced haemolysis and cytotoxicity. Reduced antimicrobial, haemolytic and cytotoxic activity was observed by increased hydrophobicity at the mid-chain. Functional improvements have been made to modified peptides when compared with native Smp24, which has produced peptides with enhanced therapeutic indices.