Violet-Pigmented Pseudomonads With Antifungal Activity From the Rhizosphere of Beans

Bean rhizosphere bacteria antagonistic to four root-infecting fungi and an antibiotic produced by these bacteria were studied. The bacteria were violet-pigmented gram-negative rods, probably belonging to the genus Pseudomonas. The antibiotic, which was localized largely in the bacterial cell mass, was easily extracted with acetone. It was selectively active against a wide variety of plant-pathogenic and saprophytic fungi tested in vitro but was relatively inactive against bacteria. The compound, partially purified by chromatography, was soluble in all organic solvents tried, but nearly insoluble in water. It demonstrated no characteristic ultraviolet- or visible-absorption spectrum and was chemically unidentified. The antagonistic bacteria or crude antibiotic applied to buried buckwheat segments suppressed the colonization of this substrate by Rhizoctonia spp. The data suggested that the bacteria or the antibiotic may play a role in the suppression of root-infecting fungi in soil.     

Discovery and Characterization of a Potent Interleukin-6 Binding Peptide with Neutralizing Activity In Vivo

Interleukin-6 (IL-6) is an important member of the cytokine superfamily, exerting pleiotropic actions on many physiological processes. Over-production of IL-6 is a hallmark of immune-mediated inflammatory diseases such as Castleman’s Disease (CD) and rheumatoid arthritis (RA). Antagonism of the interleukin IL-6/IL-6 receptor (IL-6R)/gp130 signaling complex continues to show promise as a therapeutic target. Monoclonal antibodies (mAbs) directed against components of this complex have been approved as therapeutics for both CD and RA. To potentially provide an additional modality to antagonize IL-6 induced pathophysiology, a peptide-based antagonist approach was undertaken. Using a combination of molecular design, phage-display, and medicinal chemistry, disulfide-rich peptides (DRPs) directed against IL-6 were developed with low nanomolar potency in inhibiting IL-6-induced pSTAT3 in U937 monocytic cells. Targeted PEGylation of IL-6 binding peptides resulted in molecules that retained their potency against IL-6 and had a prolongation of their pharmacokinetic (PK) profiles in rodents and monkeys. One such peptide, PN-2921, contained a 40 kDa polyethylene glycol (PEG) moiety and inhibited IL-6-induced pSTAT3 in U937 cells with sub-nM potency and possessed 23, 36, and 59 h PK half-life values in mice, rats, and cynomolgus monkeys, respectively. Parenteral administration of PN-2921 to mice and cynomolgus monkeys potently inhibited IL-6-induced biomarker responses, with significant reductions in the acute inflammatory phase proteins, serum amyloid A (SAA) and C-reactive protein (CRP). This potent, PEGylated IL-6 binding peptide offers a new approach to antagonize IL-6-induced signaling and associated pathophysiology.     

Antifungal Activity of Synthetic Scorpion Venom-Derived Peptide Analogues Against Candida albicans

International Journal of Peptide Research and Therapeutics - Fungal infections are becoming a serious problem due to their high morbidity and mortality combined with the rise in drug resistance and...     

Proteolytic Activity of the MMGP1 Antifungal Peptide Derived from Marine Metagenome

An antifungal peptide, MMGP1 with direct cell penetrating property was recently reported from marine metagenome. The peptide showed efficient in vitro proteolytic activity, which could be associated with its antifungal activity. The proteolytic activity of MMGP1 was confirmed by tricine SDS-PAGE and gel filtration chromatography. Liquid chromatography-mass spectrometry analysis of MMGP1 treated bovine serum albumin (BSA), RNaseA and casein substrates revealed that the peptide does not have common cleavage position and it cleaves the substrates non-specifically at all peptide bonds. The proteolytic activity of MMGP1 was enhanced in the presence of Mn²⁺. Molecular docking studies revealed that the predicted active site residues of MMGP1 could interact with BSA, RNaseA and casein.     

Humanin--一种新的神经保护性肽

Humanin(HN)是一种新近发现的神经保护性多肽,能够特异且有效地阻断由家族性阿尔茨海默病(FAD)基因和β淀粉样肽(Aβ)引起的细胞死亡.其作用机制可能是HN通过特异地阻断某些细胞死亡的信号通路来起到对细胞的保护作用.这些研究结果为抗阿尔茨海默病(AD)药物的研发提供了非常有价值的信息.     

Deoxygedunin,a Natural Product with Potent Neurotrophic Activity in Mice

Gedunin, a family of natural products from the Indian neem tree, possess a variety of biological activities. Here we report the discovery of deoxygedunin, which activates the mouse TrkB receptor and its downstream signaling cascades. Deoxygedunin is orally available and activates TrkB in mouse brain in a BDNF-independent way. Strikingly, it prevents the degeneration of vestibular ganglion in BDNF −/− pups. Moreover, deoxygedunin robustly protects rat neurons from cell death in a TrkB-dependent manner. Further, administration of deoxygedunin into mice displays potent neuroprotective, anti-depressant and learning enhancement effects, all of which are mediated by the TrkB receptor. Hence, deoxygedunin imitates BDNF''s biological activities through activating TrkB, providing a powerful therapeutic tool for treatment of various neurological diseases.     

Isolation and Chemical Characterization of an Alpha-Helical Peptide,Dendrocin-ZM1, Derived from Zataria multiflora Boiss with Potent Antibacterial Activity

Today, resistance of microorganisms to antibiotics has become a major challenge. To overcome this problem, development of new drugs, besides research on their antibacterial activity, is essential. Among chemical components, antimicrobial peptides (AMPs) exhibit antibacterial activity and can be selected as suitable antimicrobial candidates. In this study, a novel antimicrobial peptide, called dendrocin-ZM1, with a molecular weight of?~3716.48 Da, was isolated from Zataria multiflora Boiss (ZM) and purified via precipitation with ammonium sulfate and reverse-phase HPLC chromatography; it was then sequenced via Edman degradation. The in silico method was used to examine the physicochemical properties of dendrocin-ZM1. In this study, four reference strains (gram-positive and gram-negative) and one clinical vancomycin-resistant Staphylococcus aureus strain were used to survey the antimicrobial activities. Moreover, to examine cytotoxicity and hemolytic activity, a HEK-293 cell line and human red blood cells (RBCs) were used, respectively. Evaluation of the physicochemical properties of dendrocin-ZM1, as an AMP, indicated a net charge of?+?7 and a hydrophobicity percentage of 54%. This peptide had an amphipathic alpha-helical conformation. It exhibited broad-spectrum antibacterial activities against the tested strains at minimum inhibitory concentrations (MICs) of 4–16 μg/mL. Besides, this peptide showed negligible hemolysis and cytotoxicity in the MIC range. It also exhibited heat stability at temperatures of 20 to 80 °C and was active in a broad pH range (from 6.0 to 10.0). Overall, the present results suggested dendrocin-ZM1 as a remarkable antimicrobial candidate.

     

Novel Gallate Triphenylphosphonium Derivatives with Potent Antichagasic Activity

Chagas disease is one of the most neglected tropical diseases in the world, affecting nearly 15 million people, primarily in Latin America. Only two drugs are used for the treatment of this disease, nifurtimox and benznidazole. These drugs have limited efficacy and frequently induce adverse effects, limiting their usefulness. Consequently, new drugs must be found. In this study, we demonstrated the in vitro trypanocidal effects of a series of four gallic acid derivatives characterized by a gallate group linked to a triphenylphosphonium (TPP⁺) moiety (a delocalized cation) via a hydrocarbon chain of 8, 10, 11, or 12 atoms (TPP⁺-C₈, TPP⁺-C₁₀, TPP⁺-C₁₁, and TPP⁺-C₁₂, respectively). We analyzed parasite viability in isolated parasites (by MTT reduction and flow cytometry) and infected mammalian cells using T. cruzi Y strain trypomastigotes. Among the four derivatives, TPP⁺-C₁₀ and TPP⁺-C₁₂ were the most potent in both models, with EC₅₀ values (in isolated parasites) of 1.0 ± 0.6 and 1.0 ± 0.7 μM, respectively, and were significantly more potent than nifurtimox (EC₅₀ = 4.1 ± 0.6 μM). At 1 μM, TPP⁺-C₁₀ and TPP⁺-C₁₂ induced markers of cell death, such as phosphatidylserine exposure and propidium iodide permeabilization. In addition, at 1 μM, TPP⁺-C₁₀ and TPP⁺-C₁₂ significantly decreased the number of intracellular amastigotes (TPP⁺-C₁₀: 24.3%, TPP⁺-C₁₂: 19.0% of control measurements, as measured by DAPI staining) and the parasite’s DNA load (C₁₀: 10%, C₁₂: 13% of control measurements, as measured by qPCR). Based on the previous mode of action described for these compounds in cancer cells, we explored their mitochondrial effects in isolated trypomastigotes. TPP⁺-C₁₀ and TPP⁺-C₁₂ were the most potent compounds, significantly altering mitochondrial membrane potential at 1 μM (measured by JC-1 fluorescence) and inducing mitochondrial transition pore opening at 5 μM. Taken together, these results indicate that the TPP⁺-C₁₀ and TPP⁺-C₁₂ derivatives of gallic acid are promising trypanocidal agents with mitochondrial activity.     

A Novel Olive Oil Degrading Thermoactinomyces Species with a High Extremely Thermostable Lipase Activity

A filamentous, Gram‐positive, spore forming aerobic bacterium was isolated from olive oil contaminated soil (Al Koura, Lebanon) on rhodamine agar plates at 60 °C. The isolate, HRK‐1 produced large quantities of an extracellular thermostable lipase which degrades olive oil. It was primarily classified as a Thermoactinomyces sp. due to the filamentous structure of its cells that bear one spore each on an un‐branched sporophore, the resistance of its spores to boiling, utilisation of sucrose as a carbon source and production of dark pigments. The isolate grew optimally at a temperature of 60 °C, a pH of 7.3 and an orbital shaking of 250 rpm. It showed an efficient olive oil degrading ability. No traces of triolein were detected after a 36‐h cultivation. A concentration of 10 % [v/v] olive oil did not inhibit its growth. Lipase production was constitutive, and did not depend on the presence of olive oil. The optimum concentration of olive oil for lipase activity was 1 % [v/v], and the activity was not enhanced at higher concentrations, but on the contrary, a decrease in enzyme activity was recorded. The lipase of HRK‐1 was preliminarily characterised in the crude cell‐free supernatant with a specific activity of 0.14 U/mg. It has an optimum activity at 60 °C and a pH of 8.0. This lipolytic enzyme showed resistance to boiling and to a wide range of metallic ions and inhibitors. The formation of this heat‐stable lipase started in the early exponential growth phase, while a maximum extracellular enzyme activity was detected at the end of the decline phase, when most of the cells appeared as spherical spores. The exceptionally high activity of lipase (2.37 U/ml) produced by HRK‐1 measured in the cell free supernatant clearly indicated the commercial importance of this isolate, especially after it showed great stability at elevated temperatures.     

Cell Penetration and Secondary Structure of a Synthetic Peptide with Anti-HIV Activity

Peptidic drugs have many advantages as compared to small chemical molecules; however, they also possess some limitations as their poor membrane transducing properties. Our group has recently reported the potent anti-HIV antiviral activity of CIGB-210, a peptide derived from human keratin 10. Previous experiments showed that this peptide is internalized in MT4 cells. The aim of this study was to expand our knowledge on the uptake of CIGB-210 by assessing the peptide penetration in four other human cell lines. Cells were treated with 10, 20 and 40 µM of fluorescein-labelled CIGB-210 and the percentage of fluorescent cells was determined by flow cytometry at 15 min, 1 and 24 h. The uptake of fluorescein-labelled CIGB-210 in THP-1, HEp-2, HepG2 and PC-3 cell lines was directly proportional to both, peptide concentration and incubation times. However, some differences in the kinetics of cell entry were found. While the initial uptake was faster in HepG2 and PC-3 cells, after 24 h of incubation the percentage of fluorescence cells was equalized, although HEp-2 cells exhibited the higher numbers. The efficiency of CIGB-210 uptake was lower than a control cell penetrating peptide. However, despite the differences found, CIGB-210 was capable of transducing four human cell lines of different origins without any help. Finally, circular dichroism spectrometry data indicated that the peptide adopt a mostly disordered structure in aqueous solution, with an estimated alpha helical content of less than 5%. This study contributes to the characterization of CIGB-210 as a novel drug candidate against HIV/AIDS.     

Synthesis of New Furanone Derivatives with Potent Anticancer Activity

Russian Journal of Bioorganic Chemistry - New compounds based on Furanone derivatives were synthesized by reaction of 3-(4-nitrobezylidine)-5-phenylfuran-2(3H)-one with various reagents as...     

Plants from Brazilian Cerrado with Potent Tyrosinase Inhibitory Activity

The increased amount of melanin leads to skin disorders such as age spots, freckles, melasma and malignant melanoma. Tyrosinase is known to be the key enzyme in melanin production. Plants and their extracts are inexpensive and rich resources of active compounds that can be utilized to inhibit tyrosinase as well as can be used for the treatment of dermatological disorders associated with melanin hyperpigmentation. Using in vitro tyrosinase inhibitory activity assay, extracts from 13 plant species from Brazilian Cerrado were evaluated. The results showed that Pouteria torta and Eugenia dysenterica extracts presented potent in vitro tyrosinase inhibition compared to positive control kojic acid. Ethanol extract of Eugenia dysenterica leaves showed significant (p<0.05) tyrosinase inhibitory activity exhibiting the IC₅₀ value of 11.88 µg/mL, compared to kojic acid (IC₅₀ value of 13.14 µg/mL). Pouteria torta aqueous extract leaves also showed significant inhibitory activity with IC₅₀ value of 30.01 µg/mL. These results indicate that Pouteria torta and Eugenia dysenterica extracts and their isolated constituents are promising agents for skin-whitening or antimelanogenesis formulations.     

A Novel Time-Dependent CENP-E Inhibitor with Potent Antitumor Activity

Centromere-associated protein E (CENP-E) regulates both chromosome congression and the spindle assembly checkpoint (SAC) during mitosis. The loss of CENP-E function causes chromosome misalignment, leading to SAC activation and apoptosis during prolonged mitotic arrest. Here, we describe the biological and antiproliferative activities of a novel small-molecule inhibitor of CENP-E, Compound-A (Cmpd-A). Cmpd-A inhibits the ATPase activity of the CENP-E motor domain, acting as a time-dependent inhibitor with an ATP-competitive-like behavior. Cmpd-A causes chromosome misalignment on the metaphase plate, leading to prolonged mitotic arrest. Treatment with Cmpd-A induces antiproliferation in multiple cancer cell lines. Furthermore, Cmpd-A exhibits antitumor activity in a nude mouse xenograft model, and this antitumor activity is accompanied by the elevation of phosphohistone H3 levels in tumors. These findings demonstrate the potency of the CENP-E inhibitor Cmpd-A and its potential as an anticancer therapeutic agent.     

植物病原真菌广谱拮抗菌的筛选鉴定及发酵条件初步研究

通过对峙培养法筛选到对8种植物病原真菌具有拮抗作用的芽孢杆菌菌株,通过测量10-30℃下的抑菌圈直径发现AFB037菌株在不同温度下抑菌效果最好。通过表型和16S rDNA序列分析将AFB037菌株鉴定为多粘类芽孢杆菌。AFB037菌株抗菌成分的产生需要真菌菌体成分的诱导,提示其有效成分可能为细胞壁降解酶类。     

Synthesis of Okicamelliaside,a Glucoside of Ellagic Acid with Potent Anti-Degranulation Activity

During our scrutiny of GC-EI-MS date for C₁₅ alcohols as putative intermediates on the ABA biosynthetic pathway in Cercospora cruenta, a trace amount of 5-[2',2'-dimenthyl-6'-methylene-1'-cyclohexyl]-3-methyl-4-penten-1-ol (2,3-dihydro-γ-ionylideneethanol) was identified. Feeding experiments indicated that this compound was not an intermediate to ABA, but a catabolite that originated from γ-ionylideneacetaldehyde. The stereochemistry of 2,3-dihydro-γ-ionylideneethanol was deduced to be (3R,1'S) from a comparison with an authentic specimen prepared via baker’s yeast asymmetric reduction.     

橡胶蛋白——种与胶乳凝固有关的具有抗真菌活性的植物凝集素

 橡胶蛋白(Hevein)是一种存在于巴西橡胶树(Hevea brasiliensis)乳管细胞特化的液泡——黄色体(lutoid)内、与几丁质结合的小分子(4.7kD)单链蛋白质,在橡胶粒子的凝絮和胶乳的凝固过程中表现出极为重要的作用,是一类具有抗真菌活性的植物凝集素。     

Smp76, a Scorpine-Like Peptide Isolated from the Venom of the Scorpion Scorpio maurus palmatus,with a Potent Antiviral Activity Against Hepatitis C Virus and Dengue Virus

Growing global viral infections have been a serious public health problem in recent years. This current situation emphasizes the importance of developing m     

A New Flavanone with Antifungal Activity Isolated from Hops

6-Isopentenylnaringenin 1, which has previously been synthesized by other workers, was isolated together with xanthohumol 2 and isoxanthohumol 3 from hard resins of hops ( Humulus lupulus L.). The structures of 1 and sophoraflavanone B were examined; that of the latter previously reported as 6-isopentenylnaringenin, has been revised to 8-isopentenylnaringenin. 1, 2 and 3 were found to have antifungal activities.     

Cerbinal,a Pseudoazulene Iridoid,as a Potent Antifungal Compound Isolated from Gardenia jasminoides Ellis

d-Gluconate dehydrogenase isolated from Pseudomonas fluorescens was immobilized on the surfaces of carbon and gold electrodes by irreversible adsorption. The electrodes with the adsorbed enzyme produced anodic currents in solutions containing d-gluconate. The currents were attributable to the electro-enzymic oxidation (direct bioelectrocatalytic oxidation) of d-gluconate; the electrochemical system required no external redox molecules serving as mediators of electron transfer between the electrode and the adsorbed enzyme. A model of the direct bioelectrocatalysis at the enzyme-modified electrodes is presented.