Marine Toxins Targeting Kv1 Channels: Pharmacological Tools and Therapeutic Scaffolds.

Toxins from marine animals provide molecular tools for the study of many ion channels, including mammalian voltage-gated potassium channels of the Kv1 family. Selectivity profiling and molecular investigation of these toxins have contributed to the development of novel drug leads with therapeutic potential for the treatment of ion channel-related diseases or channelopathies. Here, we review specific peptide and small-molecule marine toxins modulating Kv1 channels and thus cover recent findings of bioactives found in the venoms of marine Gastropod (cone snails), Cnidarian (sea anemones), and small compounds from cyanobacteria. Furthermore, we discuss pivotal advancements at exploiting the interaction of κM-conotoxin RIIIJ and heteromeric Kv1.1/1.2 channels as prevalent neuronal Kv complex. RIIIJ's exquisite Kv1 subtype selectivity underpins a novel and facile functional classification of large-diameter dorsal root ganglion neurons. The vast potential of marine toxins warrants further collaborative efforts and high-throughput approaches aimed at the discovery and profiling of Kv1-targeted bioactives, which will greatly accelerate the development of a thorough molecular toolbox and much-needed therapeutics.

Tailor-made biocatalysts based on scarcely studied acidic horseradish peroxidase for biodegradation of reactive dyes.

Peroxidases (EC 1.11.1.7) have enormous biotechnological applications. Usage of more abundant, basic isoforms of peroxidases in diagnostic kits and/or in immunochemistry has led to under exploitation and disregard of horseradish peroxidase (HRP) acidic isoforms. Therefore, acidic horseradish peroxidase (HRP-A) isoenzyme was used for the preparation of a biocatalyst with improved ability in dye decolorization. Ten biocatalysts were prepared by covalent binding of enzyme to chitosan and alginate, adsorption followed by cross-linking on inorganic support (aluminum oxide), and encapsulation in spherical calcium alginate beads via polyethylene glycol. Model dyes of 50 to 175 mg l-1 were removed by the biocatalysts. Among the tested biocatalysts, the three with the highest specific activity and biodegradation rate were further studied (Chitosan-HRP, Al-Gel-HRP and Al-HRP-Gel). The impact of hydrogen peroxide concentration on dye decolorization was examined on the Chitosan-HRP biocatalyst, since the HRP is susceptible to inhibition/inactivation by high H2O2. On the other hand, H2O2 is needed as a co-substrate for the HRP, and the H2O2/dye ratio can greatly influence decolorization efficiency. Concentrations of H2O2 ranging from 0.22 to 4.4 mM showed no difference in terms of impact on the biocatalyst decolorization efficiency. The high decolorization efficiency of the biocatalysts was validated by the removal of 25 and 100 mg l-1 anthraquinone (Remazol Brilliant Blue R (RBBR)), triphenylmethane (Coomassie Brilliant Blue (CBB)), acridine (Acridine Orange (AO)), and formazan metal complex dye (Reactive Blue 52 (RB52)). After the seven consecutive decolorization cycles, the decolorization was still 53, 78, and 67% of the initial dye for the Al-HRP-Gel, Al-Gel-HRP, and Chitosan-HRP immobilizate, respectively. The results obtained showed potential of otherwise neglected acidic HRP isoforms as a cost-effective biocatalyst with significant potential in wastewater dyestuff treatment.