Impact of N-Terminal PEGylation on Synthesis and Purification of Peptide-Based Cancer Epitopes for Pancreatic Ductal Adenocarcinoma (PDAC).

Peptide-based cancer vaccines have shown promising results in preclinical trials focusing on tumor immunotherapy. However, the presence of hydrophobic amino acid segments within these peptide sequences poses challenges in their synthesis, purification, and solubility, thereby hindering their potential use as cancer vaccines. In this study, we successfully synthesized peptide sequences derived from mesothelin (MSLN), a tumor-associated antigen overexpressed in pancreatic ductal adenocarcinoma (PDAC) by conjugating them with monodisperse polyethylene glycol (PEG).

Regiodivergent Synthesis and Biological Activities of Indoloquinoline Based Compounds.

Cryptolepine, neocryptolepine, and isocryptolepine have remained popular synthetic targets ever since their isolation from the aqueous extracts of the West African climbing shrub Cryptolepis sanguinolenta. These natural alkaloids were found to contain significant antimalarial, antiproliferative and antimicrobial activities, making them ideal starting points for the development of novel drug candidates. As natural product synthesis is often plagued with step-heavy procedures and poor atom economy, the discovery of synthetic protocols addressing these concerns are sorely needed.

Transcriptomic profiles of brains in juvenile Atlantic cod (Gadus morhua) exposed to pharmaceuticals and personal care products from a wastewater treatment plant discharge.

Pharmaceuticals and personal care products (PPCPs) are frequently detected in marine environments, posing a threat to aquatic organisms. Our previous research demonstrated the occurrence of neuroactive compounds in effluent and sediments from a wastewater treatment plant (WWTP) in a fjord North of Stavanger, the fourth-largest city in Norway. To better understand the influence of PPCP mixtures on fish, Atlantic cod (Gadus morhua) were caged for one month in 3 locations: site 1 (reference), site 2 (WWTP discharge), and site 3 (6.

Changes in Plasma Pyruvate and TCA Cycle Metabolites upon Increased Hepatic Fatty Acid Oxidation and Ketogenesis in Male Wistar Rats.

Altered hepatic mitochondrial fatty acid β-oxidation and associated tricarboxylic acid (TCA) cycle activity contributes to lifestyle-related diseases, and circulating biomarkers reflecting these changes could have disease prognostic value. This study aimed to determine hepatic and systemic changes in TCA-cycle-related metabolites upon the selective pharmacologic enhancement of mitochondrial fatty acid β-oxidation in the liver, and to elucidate the mechanisms and potential markers of hepatic mitochondrial activity. Male Wistar rats were treated with 3-thia fatty acids (e.

Photodegradable antimicrobial agents: towards structure optimization.

Antibiotic resistance continues to be an ominous threat facing human health globally and urgent action is required to limit the loss of human life. The pollution of antibiotics into the environment is one of the drivers behind the crisis. With this in mind, we have developed novel photodecomposable antimicrobial agents based on an ethanolamine scaffold, which upon photoirradiation decomposes into two major inactive fragments.

Study of the long-finned pilot whale (Globicephala melas) bile content - An indicator of ocean health.

Globicephala melas has been harvested in the Faroe Islands for centuries. Given the distances travelled by this species, tissue/body fluid samples represent unique matrices to be considered as an integration of environmental condition and pollution status of their prey. For the first time, bile samples were analysed for presence of polycyclic aromatic hydrocarbon (PAH) metabolites and protein content.

The burden of emerging contaminants upon an Atlantic Ocean marine protected reserve adjacent to Camps Bay, Cape Town, South Africa.

The presence and levels of fifteen chemicals of emerging concerns, including five perfluorinated compounds (PFCs), two industrial chemicals, seven pharmaceuticals and one personal care product, were evaluated in biota, seawater and sediments obtained from near-shore coastal zone in Camps Bay, Cape Town, South Africa. Eight compounds were found in seawater, and between nine to twelve compounds were quantified in marine invertebrates, sediment and seaweed. Diclofenac was the prevalent pharmaceutical with a maximum concentration of 2.

Investigation of the enantioselectivity of acetylcholinesterase and butyrylcholinesterase upon inhibition by tacrine-iminosugar heterodimers.

The copper-catalysed azide-alkyne cycloaddition was applied to prepare three enantiomeric pairs of heterodimers containing a tacrine residue and a 1,4-dideoxy-1,4-imino-D-arabinitol (DAB) or 1,4-dideoxy-1,4-imino-L-arabinitol (LAB) moiety held together linkers of variable lengths containing a 1,2,3-triazole ring and 3, 4, or 7 CH groups. The heterodimers were tested as inhibitors of butyrylcholinesterase (BuChE) and acetylcholinesterase (AChE). The enantiomeric heterodimers with the longest linkers exhibited the highest inhibition potencies for AChE (IC = 9.

A hybrid of 1-deoxynojirimycin and benzotriazole induces preferential inhibition of butyrylcholinesterase (BuChE) over acetylcholinesterase (AChE).

The synthesis of four heterodimers in which the copper(I)-catalysed azide-alkyne cycloaddition was employed to connect a 1-deoxynojirimycin moiety with a benzotriazole scaffold is reported. The heterodimers were investigated as inhibitors against acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). The heterodimers displayed preferential inhibition (> 9) of BuChE over AChE in the micromolar concentration range (IC = 7-50 µM).

Bioaccumulation potential of the tricyclic antidepressant amitriptyline in a marine Polychaete, Nereis virens.

The continual discharge of pharmaceuticals from wastewater treatment plants (WWTPs) into the marine environment, even at concentrations as low as ng/L, can exceed levels that induce sublethal effects to aquatic organisms. Amitriptyline, a tricyclic antidepressant, is the most prescribed antidepressant in Norway, though the presence, potential for transport, and uptake by aquatic biota have not been assessed. To better understand the release and bioaccumulative capacity of amitriptyline, laboratory exposure studies were carried out with field-collected sediments.

Photodegradable Antimicrobial Agents: Synthesis and Mechanism of Degradation.

As a strategy to inactivate antimicrobial agents after use, we designed a range of ethanolamine derivatives where four of them possessed interesting activity. The ethanolamine moiety facilitates photodecomposition, which in a potential drug will take place after use. Herein, the synthetic preparation of these compounds and the mechanism of photoinactivation are described.

Photodegradable antimicrobial agents - synthesis, photodegradation, and biological evaluation.

Multi-drug resistant (MDR) bacteria are already a significant health-care problem and are making the combat of infections quite challenging. Here we report the synthesis of several new compounds containing an ethanolamine moiety, of which two exhibit promising antimicrobial activity (at the 6 μM level). All the compounds are degraded when exposed to light and form inactive products.

Substituted Two- to Five-Ring Polycyclic Aromatic Compounds Are Potent Agonists of Atlantic Cod () Aryl Hydrocarbon Receptors Ahr1a and Ahr2a.

Polycyclic aromatic hydrocarbons (PAHs) are among the most toxic and bioavailable components found in petroleum and represent a high risk to aquatic organisms. The aryl hydrocarbon receptor (Ahr) is a ligand-activated transcription factor that mediates the toxicity of 2,3,7,8-tetrachlorodibenzo--dioxin (TCDD) and other planar aromatic hydrocarbons, including certain PAHs. Ahr acts as a xenosensor and modulates the transcription of biotransformation genes in vertebrates, such as cytochrome P450 1A ().

Development of tacrine clusters as positively cooperative systems for the inhibition of acetylcholinesterase.

The synthesis of four tetra-tacrine clusters where the tacrine binding units are attached to a central scaffold linkers of variable lengths is described. The multivalent inhibition potencies for the tacrine clusters were investigated for the inhibition of acetylcholinesterase. Two of the tacrine clusters displayed a small but significant multivalent inhibition potency in which the binding affinity of each of the tacrine binding units increased up to 3.

Herbicides in Camps Bay (Cape Town, South Africa), supplemented.

During 2017 the herbicides alachlor, atrazine, butachlor, metolachlor, and simazine were detected in water samples, beach sediments and marine biota collected at Camps Bay, Cape Town, South Africa. During that period, the annual rain catchment record was 77,000 m, whereas the volume of chemically laden sewage discharged via the marine outfall was 693,500 m making the marine sewage outfall by far the most predominant source for these herbicides in the bay. The chemical load in the discharged sewage was not removed by the applied pre-treatment step, which only uses a 3 mm screen to eliminate plastic, paper, rags and other foreign materials.

Tacrine-sugar mimetic conjugates as enhanced cholinesterase inhibitors.

We have used the Cu(i)-catalyzed azide-alkyne Huisgen cycloaddition reaction to obtain two families of bivalent heterodimers where tacrine is connected to an azasugar or iminosugar, respectively, via linkers of variable length. The heterodimers were investigated as cholinesterase inhibitors and it was found that their activity increased with the length of the linker. Two of the heterodimers were significantly stronger acetylcholinesterase inhibitors than the monomeric tacrine.

Synthesis of the Hexahydropyrrolo-[3,2-c]-quinoline Core Structure and Strategies for Further Elaboration to Martinelline, Martinellic Acid, Incargranine B, and Seneciobipyrrolidine.

Natural products are rich sources of interesting scaffolds possessing a plethora of biological activity. With the isolation of the martinella alkaloids in 1995, namely martinelline and martinellic acid, the pyrrolo[3,2-c]quinoline scaffold was discovered. Since then, this scaffold has been found in two additional natural products, viz.

Presence and risk assessment of herbicides in the marine environment of Camps Bay (Cape Town, South Africa).

The present study was conducted during a time of drought to assess the concentration of herbicides and their potential for accumulation in marine biota found in the near shore marine environment of an urban setting (Camps Bay, Cape Town, South Africa). The purpose was to establish whether raw sewage containing selected persistent chemicals that are released through a local marine outfall would be sufficiently diluted by the ocean to prevent impact on the near-shore marine environment of the suburb Camps Bay. Samples of seawater, sediment, seaweed, and selected marine organisms present in the near shore environment, such as limpets (Cymbula granatina), mussels (Mytilus galloprovincialis), and sea urchins (Parechinus angulosus), were analysed for five indicator herbicides, namely atrazine, alachlor, simazine, metolachlor, and butachlor, with gas chromatography coupled with a mass spectrometer.

1,4-Dideoxy-1,4-imino-d-arabinitol (DAB) Analogues Possessing a Hydrazide Imide Moiety as Potent and Selective α-Mannosidase Inhibitors.

The synthesis of two polyhydroxylated pyrrolidines as 1,4-dideoxy-1,4-imino-d-arabinitol (DAB) analogues bearing a hydrazide moiety is described. The DAB analogues act as selective and potent inhibitors of α-mannosidase in the submicromolar concentration ranges ( values ranging from 0.23 to 1.

Synthesis of trans-dihydronaphthalene-diols and evaluation of their use as standards for PAH metabolite analysis in fish bile by GC-MS.

Phenols and trans-1,2-dihydro-1,2-diols are metabolites commonly formed in vivo in fish upon exposure to polycyclic aromatic hydrocarbons (PAHs). These metabolites are excreted via the bile and gas chromatography-mass spectrometry (GC-MS) analysis of bile is becoming more frequently used for evaluating PAH exposure levels in fish. Current protocols focus on the detection and quantification of phenols formed during in vivo oxidation of PAHs, leaving out analyses and quantification of other oxidation products such as trans-1,2-dihydro-1,2-diols, potentially underestimating exposure levels.

Synthesis of an Alleged Byproduct Precursor in Iodixanol Preparation.

, -Bis(2,3-dihydroxypropyl)-2,4,6-triiodo-5-(-(oxiran-2-ylmethyl)acetamido)isophthalamide (), the alleged precursor of several minor byproducts formed when the X-ray contrast agent iodixanol is synthesized from 5-acetamido- , -bis(2,3-dihydroxypropyl)-2,4,6-triiodoisophthalamide (), has been successfully prepared with an overall yield of 25%. Epoxide enabled the confirmation of its presence in the reaction mixture during the preparation of iodixanol when amide was used as the starting material.

The crystal structure of haemoglobin from Atlantic cod.

The crystal structure of haemoglobin from Atlantic cod has been solved to 2.54 Å resolution. The structure consists of two tetramers in the crystallographic asymmetric unit.