Unlabelled: has become the causal agent of multiple forms of gastric disease worldwide, including gastric cancer. The enzyme l-asparaginase (ASNase) has been studied as a virulence factor. In this work, we performed an in silico investigation to characterize the immunological profile of ASNase (HpASNase) to ascertain the possible implication of HpASNase immunogenicity in the virulence mechanism.
View Article and Find Full Text PDFPhage display links the phenotype of displayed polypeptides with the DNA sequence in the phage genome and offers a universal method for the discovery of proteins with novel properties. However, the display of large multisubunit proteins on phages remains a challenge. A majority of protein display systems are based on monovalent phagemid constructs, but methods for the robust display of multiple copies of large proteins are scarce.
View Article and Find Full Text PDFPolymersomes are versatile nanostructures for protein delivery with hydrophilic core suitable for large biomolecule encapsulation and protective stable corona. Nonetheless, pharmaceutical products based on polymersomes are not available in the market, yet. Here, using commercially available copolymers, we investigated the encapsulation of the active pharmaceutical ingredient (API) L-asparaginase, an enzyme used to treat acute lymphoblastic leukemia, in polymersomes through a quality-by-design (QbD) approach.
View Article and Find Full Text PDFAcute lymphoblastic leukemia (ALL) is a type of cancer with a high incidence in children. The enzyme l-asparaginase (ASNase) constitutes a key element in the treatment of this disease. Four formulations of ASNase from a bacterial source are currently available.
View Article and Find Full Text PDFL-asparaginase (ASNase) from Escherichia coli is currently used in some countries in its PEGylated form (ONCASPAR, pegaspargase) to treat acute lymphoblastic leukemia (ALL). PEGylation refers to the covalent attachment of poly(ethylene) glycol to the protein drug and it not only reduces the immune system activation but also decreases degradation by plasmatic proteases. However, pegaspargase is randomly PEGylated and, consequently, with a high degree of polydispersity in its final formulation.
View Article and Find Full Text PDFCrisantaspase is an asparaginase enzyme produced by Erwinia chrysanthemi and used to treat acute lymphoblastic leukemia (ALL) in case of hypersensitivity to Escherichia coli l-asparaginase (ASNase). The main disadvantages of crisantaspase are the short half-life (10 H) and immunogenicity. In this sense, its PEGylated form (PEG-crisantaspase) could not only reduce immunogenicity but also improve plasma half-life.
View Article and Find Full Text PDFThe dopamine hypothesis states that decreased dopaminergic neurotransmission reduces schizophrenia symptoms. Neurokinin-3 receptor (NK3) antagonists reduce dopamine release and have shown positive effects in pre-clinical and clinical trials. We employed 2D and 3D-QSAR analysis on a series of 40 non-peptide NK3 antagonists.
View Article and Find Full Text PDFCoarse-grained molecular dynamics simulations are used to calculate the free energies of transfer of miltefosine, an alkylphosphocholine anticancer agent, from water to lipid bilayers to study its mechanism of interaction with biological membranes. We consider bilayers containing lipids with different degrees of unsaturation: dipalmitoylphosphatidylcholine (DPPC, saturated, containing 0%, 10%, and 30% cholesterol), dioleoylphosphatidylcholine (DOPC, diunsaturated), palmitoyloleoylphosphatidylcholine (POPC, monounsaturated), diarachidonoylphosphatidylcholine (DAPC, polyunsaturated), and dilinoleylphosphatidylcholine (DUPC, polyunsaturated). These free energies, calculated using umbrella sampling, were used to compute the partition coefficients (K) of miltefosine between water and the lipid bilayers.
View Article and Find Full Text PDFPurpose: Since when alkylphospholipds (ALPs) were discovered and, even further after miltefosine's approval for the treatment of cutaneous metastasis of breast cancer and leishmaniasis, their activity against many other diseases have been extensively studied. This review aims to provide a summary of the alkylphospholipids' applications investigated so far.
Results: The mechanism of action of ALPs is not fully understood, however it is believed that they interfere with lipid homeostasis leading to cell apoptosis.
The effects of light intensity and temperature in S. platensis cultivation with potassium nitrate or urea as nitrogen source were investigated, as well as the biomass chlorophyll contents of this cyanobacteria, through the Response Surface Methodology. Experiments were performed at temperatures from 25 to 34.
View Article and Find Full Text PDFNitrofurazone (NF) and its derivative, hydroxymethylnitrofurazone (NFOH), have presented antichagasic activity. NFOH has higher activity and lower mutagenicity. The aim of this work was to assess whether NF and its derivative NFOH would also be inhibitors of cruzain, besides their trypanothione reductase inhibitory activity.
View Article and Find Full Text PDFMolecular modification is a quite promising strategy in the design and development of drug analogs with better bioavailability, higher intrinsic activity and less toxicity. In the search of new leads with potential antimicrobial activity, a new series of 14 4-substituted [N'-(benzofuroxan-5-yl)methylene]benzohydrazides, nifuroxazide derivatives, were synthesized and tested against standard and multidrug-resistant Staphylococcus aureus strains. The selection of the substituent groups was based on physicochemical properties, such as hydrophobicity and electronic effect.
View Article and Find Full Text PDFPurpose: Micellar solubilization is a powerful alternative for dissolving hydrophobic drugs in aqueous environments. In this work, we provide an insight into this subject.
Methods: A concise review of surfactants and micelles applications in pharmacy was carried out.