The Multiple Uses of Polypropylene/Polyethylene Terephthalate Microfibrillar Composite Structures to Support Waste Management-Composite Processing and Properties.

Composite processing and subsequent characterization of microfibrillar composites (MFC) were the focus of this work. Compression molding of wound MFC filaments was used to fabricate MFC composites. The MFC composites were composed of polypropylene (PP) as matrix materials and polyethylene terephthalate (PET) as reinforcement fibers.

Development of Polypropylene/Polyethylene Terephthalate Microfibrillar Composites Filament to Support Waste Management.

The concept of microfibrillar composites (MFCs) is adopted to produce composites of polyethylene terephthalate (PET) fiber-reinforced polypropylene (PP) materials. The two polymers were dry mixed with PET content ranging from 22 to 45 wt%. The PET has been used as a reinforcement to improve the mechanical properties of composites.

The antioxidative effect of de novo generated vitamin B6 in Plasmodium falciparum validated by protein interference.

The malaria parasite Plasmodium falciparum is able to synthesize de novo PLP (pyridoxal 5'-phosphate), the active form of vitamin B6. In the present study, we have shown that the de novo synthesized PLP is used by the parasite to detoxify 1O2 (singlet molecular oxygen), a highly destructive reactive oxygen species arising from haemoglobin digestion. The formation of 1O2 and the response of the parasite were monitored by live-cell fluorescence microscopy, by transcription analysis and by determination of PLP levels in the parasite.

Facile synthesis and in-vitro antimalarial activity of novel α-hydroxy hydrazonates.

A series of previously unreported α-hydroxy hydrazonates were synthesized and tested for their antimalarial properties. Structure optimization of the antiplasmodially active α-hydroxy hydrazonate III furnished derivatives with strong in-vitro antimalarial activity against 3D7 strains of Plasmodium falciparum with IC(50) values lower than 2.0 µM.

Secretion of an acid phosphatase provides a possible mechanism to acquire host nutrients by Plasmodium falciparum.

As an intracellular proliferating parasite, Plasmodium falciparum exploits the human host to acquire nutrients. However, nutrients such as nucleotides and cofactors are mostly phosphorylated in the host cell cytosol and thus have to be dephosphorylated in order to be taken up by the parasite. Here we report the functional characterization of a unique secreted phosphatase in P.

The vitamin B1 metabolism of Staphylococcus aureus is controlled at enzymatic and transcriptional levels.

Vitamin B1 is in its active form thiamine pyrophosphate (TPP), an essential cofactor for several key enzymes in the carbohydrate metabolism. Mammals must salvage this crucial nutrient from their diet in order to complement the deficiency of de novo synthesis. In the human pathogenic bacterium Staphylococcus aureus, two operons were identified which are involved in vitamin B1 metabolism.

Poisoning pyridoxal 5-phosphate-dependent enzymes: a new strategy to target the malaria parasite Plasmodium falciparum.

The human malaria parasite Plasmodium falciparum is able to synthesize de novo pyridoxal 5-phosphate (PLP), a crucial cofactor, during erythrocytic schizogony. However, the parasite possesses additionally a pyridoxine/pyridoxal kinase (PdxK) to activate B6 vitamers salvaged from the host. We describe a strategy whereby synthetic pyridoxyl-amino acid adducts are channelled into the parasite.

Purification and biochemical characterization of cytosolic glutathione-S-transferase from filarial worms Setaria cervi.

The present study reports the purification and characterization of GST from cytosolic fraction of Setaria cervi. GST activity was determined in various subcellular fractions of bovine filarial worms S. cervi (Bubalus bubalis Linn.

Assessing the polyamine metabolism of Plasmodium falciparum as chemotherapeutic target.

More than 30 years ago the potent ornithine decarboxylase inhibitor difluoromethylornithine (DFMO) was designed as new anticancer drug. Its efficacy was not as expected since the polyamine metabolism in mammalian cells seemed to be far more complex. However when DFMO was applied to African trypanosomes its effect on this protozoan parasite was highly convincing.

The assembly of the plasmodial PLP synthase complex follows a defined course.

Background: Plants, fungi, bacteria and the apicomplexan parasite Plasmodium falciparum are able to synthesize vitamin B6 de novo, whereas mammals depend upon the uptake of this essential nutrient from their diet. The active form of vitamin B6 is pyridoxal 5-phosphate (PLP). For its synthesis two enzymes, Pdx1 and Pdx2, act together, forming a multimeric complex consisting of 12 Pdx1 and 12 Pdx2 protomers.

Filling the gap of intracellular dephosphorylation in the Plasmodium falciparum vitamin B1 biosynthesis.

Thiamine pyrophosphate (TPP), the active form of vitamin B1, is an essential cofactor for several enzymes. Humans depend exclusively on the uptake of vitamin B1, whereas bacteria, plants, fungi and the malaria parasite Plasmodium falciparum are able to synthesise thiamine monophosphate (TMP) de novo. TMP has to be dephosphorylated prior to pyrophosphorylation in order to obtain TPP.

gamma-Substituted bis(pivaloyloxymethyl)ester analogues of fosmidomycin and FR900098.

The synthesis and in-vitro antimalarial activity of gamma-substituted bis(pivaloyloxymethyl)ester analogues of the drug candidate fosmidomycin have been investigated. In contrast to the high antimalarial activity of alpha-aryl substituted fosmidomycin analogues like alpha-phenylfosmidomycin, gamma-substituted derivatives display only weak to moderate activity against the chloroquine-sensitive strain 3D7 of Plasmodium falciparum.

Oxidative stress in Caenorhabditis elegans: protective effects of the Omega class glutathione transferase (GSTO-1).

To elucidate the function of Omega class glutathione transferases (GSTs) (EC 2.5.1.

Crystal structure of Plasmodium falciparum spermidine synthase in complex with the substrate decarboxylated S-adenosylmethionine and the potent inhibitors 4MCHA and AdoDATO.

Plasmodium falciparum is the causative agent of the most severe type of malaria, a life-threatening disease affecting the lives of over three billion people. Factors like widespread resistance against available drugs and absence of an effective vaccine are seriously compounding control of the malaria parasite. Thus, there is an urgent need for the identification and validation of new drug targets.

Synthesis and biological evaluation of potential modulators of malarial glutathione-S-transferase(s).

Glutathione-S-transferase(s) (E.C.2.

Conformationally restrained aromatic analogues of fosmidomycin and FR900098.

The synthesis and in-vitro antimalarial activity of conformationally restrained bis(pivaloyloxymethyl) ester analogues of the natural product fosmidomycin is presented. In contrast to alpha-aryl-substituted analogues, conformationally restrained aromatic analogues exhibit only moderate in-vitro antimalarial activity against the chloroquine-sensitive strain 3D7 of Plasmodium falciparum. The most active derivative displays an IC(50) value of 47 microM.

Structural and mechanistic insights into the action of Plasmodium falciparum spermidine synthase.

Spermidine synthase is currently considered as a promising drug target in the malaria parasite, Plasmodium falciparum, due to the vital role of spermidine in the activation of the eukaryotic translation initiation factor (eIF5A) and cell proliferation. However, very limited information was available regarding the structure and mechanism of action of the protein at the start of this study. Structural and mechanistic insights of the P.

The human malaria parasite Plasmodium falciparum expresses an atypical N-terminally extended pyrophosphokinase with specificity for thiamine.

Vitamin B(1) is an essential cofactor for key enzymes such as 2-oxoglutarate dehydrogenase and pyruvate dehydrogenase. Plants, bacteria and fungi, as well as Plasmodium falciparum, are capable of synthesising vitamin B(1)de novo, whereas mammals have to take up this cofactor from their diet. Thiamine, a B(1) vitamer, has to be pyrophosphorylated by thiamine pyrophosphokinase (TPK) to the active form.

Arylmethyl substituted derivatives of Fosmidomycin: synthesis and antimalarial activity.

The phosphonohydroxamic acid Fosmidomycin is a drug candidate for the treatment of Malaria, currently in phase II trials in combination with Clindamycin. In order to obtain compounds of higher lipophilicity, we recently synthesized alpha-phenyl substituted Fosmidomycin derivatives which display high antimalarial activity. We now report the synthesis and in vitro antimalarial activity of arylmethyl substituted bis(pivaloyloxymethyl) ester prodrugs of Fosmidomycin and its acetyl analogue FR900098.

Synthesis and antimalarial activity of chain substituted pivaloyloxymethyl ester analogues of Fosmidomycin and FR900098.

Fosmidomycin is a promising antimalarial drug candidate with a unique chemical structure and a novel mode of action. Chain substituted pivaloyloxymethyl ester derivatives of Fosmidomycin and its acetyl analogue FR900098 have been synthesized and their in vitro antimalarial activity versus the Chloroquine sensitive strain 3D7 of Plasmodium falciparum has been determined.

Vitamin B1 de novo synthesis in the human malaria parasite Plasmodium falciparum depends on external provision of 4-amino-5-hydroxymethyl-2-methylpyrimidine.

Vitamin B1 (thiamine) is an essential cofactor for several key enzymes of carbohydrate metabolism. Mammals have to salvage this crucial nutrient from their diet to complement their deficiency of de novo synthesis. In contrast, bacteria, fungi, plants and, as reported here, Plasmodium falciparum, possess a vitamin B1 biosynthesis pathway.

Novel properties of malarial S-adenosylmethionine decarboxylase as revealed by structural modelling.

In the malaria parasite, the two main regulatory activities of polyamine biosynthesis, ornithine decarboxylase (ODC) and S-adenosylmethionine decarboxylase (AdoMetDC) occur in a single bifunctional protein. The AdoMetDC domain was modeled using the human and potato X-ray crystal structures as templates. Three parasite-specific inserts and the core active site region was identified using a structure-based alignment approach.

Cloning, expression, characterisation and three-dimensional structure determination of Caenorhabditis elegans spermidine synthase.

The polyamine synthesis enzyme spermidine synthase (SPDS) has been cloned from the model nematode Caenorhabditis elegans. Biochemical characterisation of the recombinantly expressed protein revealed a high degree of similarity to other eukaryotic SPDS with the exception of a low affinity towards the substrate decarboxylated S-adenosylmethionine (Km = 110 microM) and a less pronounced feedback inhibition by the second reaction product 5'-methylthioadenosine (IC50 = 430 microM). The C.

The highly abundant protein Ag-lbp55 from Ascaridia galli represents a novel type of lipid-binding proteins.

Lipid-binding proteins exhibit important functions in lipid transport, cellular signaling, gene transcription, and cytoprotection. Their functional analogues in nematodes are nematode polyprotein allergens/antigens and fatty acid and retinoid-binding proteins. This work describes a novel 55-kDa protein, Ag-lbp55, purified from the parasitic nematode Ascaridia galli.