Prevention of amyloid β fibril deposition on the synaptic membrane in the precuneus by ganglioside nanocluster-targeting inhibitors.

Alzheimer's disease (AD), a progressive neurodegenerative condition, is one of the most common causes of dementia. Senile plaques, a hallmark of AD, are formed by the accumulation of amyloid β protein (Aβ), which starts to aggregate before the onset of the disease. Gangliosides, sialic acid-containing glycosphingolipids, play a key role in the formation of toxic Aβ aggregates.

Cyclization of Peptides Enhances the Inhibitory Activity against Ganglioside-Induced Aβ Fibril Formation.

Alzheimer's disease is a progressive neurodegenerative disease and is the most common cause of dementia. It has been reported that the assembly of amyloid β-protein (Aβ) on the cell membrane is induced by the interaction of the Aβ monomer with gangliosides such as GM1. The ganglioside-bound Aβ (GAβ) complex acts as a seed to promote the toxic assembly of the Aβ fibrils.

Effects of the Magnetic Orientation of M13 Bacteriophage on Phage Display Selection.

Although phage display selection using a library of M13 bacteriophage has become a powerful tool for finding peptides that bind to target materials on demand, a remaining concern of this method is the interference by the M13 main body, which is a huge filament >10  times larger than the displayed peptide, and therefore would nonspecifically adhere to the target or sterically inhibit the binding of the displayed peptide. Meanwhile, filamentous phages are known to be orientable by an external magnetic field. If M13 filaments are magnetically oriented during the library selection, their angular arrangement relative to the target surface would be changed, being expected to control the interference by the M13 main body.

Endocytosis-Like Vesicle Fission Mediated by a Membrane-Expanding Molecular Machine Enables Virus Encapsulation for In Vivo Delivery.

Biological membranes are functionalized by membrane-associated protein machinery. Membrane-associated transport processes, such as endocytosis, represent a fundamental and universal function mediated by membrane-deforming protein machines, by which small biomolecules and even micrometer-size substances can be transported via encapsulation into membrane vesicles. Although synthetic molecules that induce dynamic membrane deformation have been reported, a molecular approach enabling membrane transport in which membrane deformation is coupled with substance binding and transport remains critically lacking.

The sialyl-Tn antigen synthase genes regulates migration-proliferation dichotomy in prostate cancer cells under hypoxia.

A low-oxygen (hypoxia) tumor microenvironment can facilitate chemotherapy and radiation therapy resistance in tumors and is associated with a poor prognosis. Hypoxia also affects PCa (prostate cancer) phenotype transformation and causes therapeutic resistance. Although O-glycans are known to be involved in the malignancy of various cancers under hypoxia, the expression and function of O-glycans in PCa are not well understood.

Dihydromaniwamycin E, a Heat-Shock Metabolite from Thermotolerant sp. JA74, Exhibiting Antiviral Activity against Influenza and SARS-CoV-2 Viruses.

Dihydromaniwamycin E (), a new maniwamycin derivative featuring an azoxy moiety, has been isolated from the culture extract of thermotolerant sp. JA74 along with the known analogue maniwamycin E (). Compound is produced only by cultivation of strain JA74 at 45 °C, and this type of compound has been previously designated a "heat shock metabolite (HSM)" by our research group.

Effective Cell Transfection in An Ultrasonically Levitated Droplet for Sustainable Technology.

The levitation methodology, which enables us to operate a contactless reaction without a container, is likely to be a revolutionary technology in the fields of chemistry and biology to reduce the plastic waste in life science laboratories. Here, the authors show that plasmid DNA can be effectively transfected into animal cells in a floating droplet of culture medium levitated using ultrasonic standing waves. The data indicate that there is no significant damage to the plasmid and cells during the levitating transfection time, and the transgene expression efficiency and cellular uptake in the droplet are significantly higher than those in the conventional tube, with and without shaking.

Functional analysis of GCNT3 for cell migration and EMT of castration-resistant prostate cancer cells.

Castration-resistant prostate cancer (CRPC) is a malignant tumor that is resistant to androgen deprivation therapy. Treatments for CRPC are limited, and no diagnostic markers are currently available. O-glycans are known to play an important role in cell proliferation, migration, invasion, and metastasis of cancer cells.

Ganglioside Nanocluster-Targeting Peptidyl Inhibitor Prevents Amyloid β Fibril Formation on the Neuronal Membrane.

Neurotoxicity caused by peptide and protein aggregates is associated with the onset of neurodegenerative diseases. Accumulation of the amyloid β protein (Aβ) induced by neuronal ganglioside-enriched nanodomains (nanoclusters) in the presynaptic neuronal membrane, resulting in toxic oligomeric and fibrous forms, is implicated in the onset of Alzheimer's disease (AD). In the current study, we found that the ganglioside cluster-binding peptide (GCBP), a pentadecapeptide VWRLLAPPFSNRLLP that binds to ganglioside-enriched nanoclusters, inhibits the formation of Aβ assemblies with an IC of 12 pM and also removes Aβ fibrils deposited on the lipid membrane.

Detection of Influenza Virus by Agglutination of Microparticles Immobilized a Mixed Glycan Receptor Produced from Cells.

The hemagglutination inhibition (HAI) assay is one of the detection methods for influenza virus (IFV) under global influenza surveillance, which uses freshly prepared animal red blood cells (RBCs). Here, we demonstrate that a mixed glycan-modified polystyrene microparticle, which can be chemically prepared in advance, can replace animal RBCs in the HAI assay. A mixture of azide-conjugated glycans containing sialyl- and sulfated-lactose moieties was produced from Madin-Darby canine kidney (MDCK) cells, which are used for IFV isolation, and then immobilized on the surface of a polystyrene microparticle using click chemistry.

In vitro synthesis of mucin-type O-glycans using saccharide primers comprising GalNAc-Ser and GalNAc-Thr residues.

Mucin-type O-glycosylation of serine or threonine residue in proteins is known to be one of the major post-translational modifications. In this study, two novel alkyl glycosides, N-lauryl-O-(2-acetamido-2-deoxy-α-d-galactopyranosyl)-l-serineamide (GalNAc-Ser-C12) and N-lauryl-O-(2-acetamido-2-deoxy-α-d-galactopyranosyl)-l-threonineamide (GalNAc-Thr-C12) were synthesized as saccharide primers to prime mucin-type O-glycan biosynthesis in cells. Upon incubating human gastric cancer MKN45 cells with the saccharide primers, 22 glycosylated products were obtained, and their structures were analyzed using liquid chromatography-mass spectrometry and enzyme digestion.

Motobamide, an Antitrypanosomal Cyclic Peptide from a sp. Marine Cyanobacterium.

Motobamide (), a new cyclic peptide containing a -prenylated cyclotryptophan residue, was isolated from a marine sp. cyanobacterium. Its planar structure was established by spectroscopic and MS/MS analyses.

Heterogeneous Ganglioside-Enriched Nanoclusters with Different Densities in Membrane Rafts Detected by a Peptidyl Molecular Probe.

The specific features of the lateral distribution of gangliosides play key roles in cell-cell communications and the onset of various diseases related to the plasma membrane. We herein demonstrated that an artificial peptide identified from a phage-displayed library is available as a molecular probe for specific ganglioside nanoclustering sites in caveolae/membrane rafts on the cell surface. Atomic force microscopy studies indicated that the peptide specifically binds to the highly enriched monosialoganglioside GM1 nanodomains of reconstituted lipid bilayers composed of GM1, sphingomyelin, cholesterol, and unsaturated phospholipids.

Avian Influenza Virus Detection by Optimized Peptide Termination on a Boron-Doped Diamond Electrode.

The development of a simple detection method with high sensitivity is essential for the diagnosis and surveillance of infectious diseases. Previously, we constructed a sensitive biosensor for the detection of pathological human influenza viruses using a boron-doped diamond electrode terminated with a sialyloligosaccharide receptor-mimic peptide that could bind to hemagglutinins involved in viral infection. Circulation of influenza induced by the avian virus in humans has become a major public health concern, and methods for the detection of avian viruses are urgently needed.

Ikoamide, an Antimalarial Lipopeptide from an sp. Marine Cyanobacterium.

An antimalarial lipopeptide, ikoamide, was isolated from an sp. marine cyanobacterium. Its gross structure was established by spectroscopic analyses, and the absolute configuration was clarified based on a combination of chiral-phase HPLC analyses, spectroscopic analyses, and derivatization reactions.

Synthesis of Various Glycopolymers Bearing Sialyllactose and the Effect of Their Molecular Mobility on Interaction with the Influenza Virus.

Synthetic glyco-ligands are promising candidates for effective nanomedicines against pathogens. Glycopolymers bearing sialyl-oligosaccharides interact with hemagglutinin present on the surface of influenza viruses. In designing new glycopolymers that further enhance the interaction with viruses, both static and dynamic properties of the glycopolymers should be considered.

Topological Design of Star Glycopolymers for Controlling the Interaction with the Influenza Virus.

The precise design of synthetic polymer ligands using controlled polymerization techniques provides an advantage for the field of nanoscience. We report the topological design of glyco-ligands based on synthetic polymers for targeting hemagglutinin (HA, lectin on the influenza virus). To achieve precise arrangement of the glycounits toward the sugar-binding pockets of HA, triarm star glycopolymers were synthesized.

Hoshinoamides A and B, Acyclic Lipopeptides from the Marine Cyanobacterium Caldora penicillata.

Hoshinoamides A (1) and B (2), new acyclic lipopeptides, were isolated from the marine cyanobacterium Caldora penicillata. Their structures were elucidated by spectroscopic analyses and degradation reactions. Hoshinoamides A (1) and B (2) did not exhibit any cytotoxicity against HeLa cells at 10 μM, but inhibited the in vitro growth of the malarial parasite Plasmodium falciparum (IC = 0.

Saccharide Primers Comprising Xylosyl-Serine Primed Phosphorylated Oligosaccharides Act as Intermediates in Glycosaminoglycan Biosynthesis.

β-Xylosides have been used as an artificial initiator of glycosaminoglycan (GAG) biosynthesis to investigate its mechanism and to obtain these oligosaccharides. In GAG biosynthesis, phosphorylation on the xylose residue is a crucial step. However, little attention has been paid to phosphorylated oligosaccharides obtained from β-xylosides.

Amyloid-β fibrils assembled on ganglioside-enriched membranes contain both parallel β-sheets and turns.

Some protein and peptide aggregates, such as those of amyloid-β protein (Aβ), are neurotoxic and have been implicated in several neurodegenerative diseases. Aβ accumulates at nanoclusters enriched in neuronal lipids called gangliosides in the presynaptic neuronal membrane, and the resulting oligomeric and/or fibrous forms accelerate the development of Alzheimer's disease. Although the presence of Aβ deposits at such nanoclusters is known, the mechanism of their assembly and the relationship between Aβ secondary structure and topography are still unclear.

Izenamides A and B, Statine-Containing Depsipeptides, and an Analogue from a Marine Cyanobacterium.

Izenamides A, B, and C (1-3), new linear depsipeptides, were isolated from a taxonomically distinct marine cyanobacterium. Izenamides A and B contain a statine moiety [(3 S,4 S)-4-amino-3-hydroxy-6-methylheptanoic acid] and inhibited the activity of cathepsin D, an aspartic peptidase. Meanwhile, izenamides did not show growth-inhibitory activity against HeLa, HL60, or MCF-7 cells at up to 10 μM.