Early diagnosis and treatment of Alzheimer's disease by targeting toxic soluble Aß oligomers.

Transient soluble oligomers of amyloid-ß (Aß) are toxic and accumulate early prior to insoluble plaque formation and cognitive impairment in Alzheimer's disease (AD). Synthetic cyclic D,L-α-peptides (e.g., 1) self-assemble into cross ß-sheet nanotubes, react with early Aß species (1-3 mers), and inhibit Aß aggregation and toxicity in stoichiometric concentrations, in vitro. Employing a semicarbazide as an aza-glycine residue with an extra hydrogen-bond donor to tune nanotube assembly and amyloid engagement, [azaGly6]-1 inhibited Aß aggregation and toxicity at substoichiometric concentrations. High-resolution NMR studies revealed dynamic interactions between [azaGly6]-1 and Aß42 residues F19 and F20, which are pivotal for early dimerization and aggregation. In an AD mouse model, brain positron emission tomography (PET) imaging using stable 64Cu-labeled (aza)peptide tracers gave unprecedented early amyloid detection in 44-d presymptomatic animals. No tracer accumulation was detected in the cortex and hippocampus of 44-d-old 5xFAD mice; instead, intense PET signal was observed in the thalamus, from where Aß oligomers may spread to other brain parts with disease progression. Compared with standard 11C-labeled Pittsburgh compound-B (11C-PIB), which binds specifically fibrillar Aß plaques, 64Cu-labeled (aza)peptide gave superior contrast and uptake in young mouse brain correlating with Aß oligomer levels. Effectively crossing the blood-brain barrier (BBB), peptide 1 and [azaGly6]-1 reduced Aß oligomer levels, prolonged lifespan of AD transgenic Caenorhabditis elegans, and abated memory and behavioral deficits in nematode and murine AD models. Cyclic (aza)peptides offer novel promise for early AD diagnosis and therapy.

Multifunctional Liposomes Targeting Amyloid-ß Oligomers for Early Diagnosis and Therapy of Alzheimer's Disease.

Early detection and treatment are crucial for Alzheimer's disease (AD) management. Current diagnostic and therapeutic methods focus on late-stage amyloid fibrils and plaques, overlooking toxic soluble amyloid ß oligomers (AßOs) accumulating early in AD. A multifunctional liposome-based platform is designed for early diagnosis and therapy of AD, leveraging a novel self-assembled cyclic d,l-α-peptide (CP-2) that selectively targets AßOs. Biocompatible CP-2 conjugated liposomes (CP-2-LPs) effectively disrupt Aß aggregation and mitigate Aß-mediated toxicity in human neuroblastoma cells. In transgenic Caenorhabditis elegans AD models, CP-2-LPs significantly outperformed free CP-2 by improving cognitive and behavioral functions, extending lifespan, and reducing toxic AßO levels. Intravenous injection of fluorescently labeled CP-2-LPs reveals effective blood-brain barrier penetration, with significantly higher brain fluorescence in transgenic mice than WT, enabling precise diagnosis. These findings underscore CP-2-LPs as a valuable tool for early detection and targeted therapy in AD.

Cu2+-Induced self-assembly and amyloid formation of a cyclic D,L-α-peptide: structure and function.

In a wide spectrum of neurodegenerative diseases, self-assembly of pathogenic proteins to cytotoxic intermediates is accelerated by the presence of metal ions such as Cu2+. Only low concentrations of these early transient oligomeric intermediates are present in a mixture of species during fibril formation, and hence information on the extent of structuring of these oligomers is still largely unknown. Here, we investigate dimers as the first intermediates in the Cu2+-driven aggregation of a cyclic D,L-α-peptide architecture. The unique structural and functional properties of this model system recapitulate the self-assembling properties of amyloidogenic proteins including ß-sheet conformation and cross-interaction with pathogenic amyloids. We show that a histidine-rich cyclic D,L-α-octapeptide binds Cu2+ with high affinity and selectivity to generate amyloid-like cross-ß-sheet structures. By taking advantage of backbone amide methylation to arrest the self-assembly at the dimeric stage, we obtain structural information and characterize the degree of local order for the dimer. We found that, while catalytic amounts of Cu2+ promote aggregation of the peptide to fibrillar structures, higher concentrations dose-dependently reduce fibrillization and lead to formation of spherical particles, showing self-assembly to different polymorphs. For the initial self-assembly step to the dimers, we found that Cu2+ is coordinated on average by two histidines, similar to self-assembled peptides, indicating that a similar binding interface is perpetuated during Cu2+-driven oligomerization. The dimer itself is found in heterogeneous conformations that undergo dynamic exchange, leading to the formation of different polymorphs at the initial stage of the aggregation process.

Neuroprotective Effect of Nerve Growth Factor Loaded in Porous Silicon Nanostructures in an Alzheimer's Disease Model and Potential Delivery to the Brain.

Nerve growth factor (NGF) plays a vital role in reducing the loss of cholinergic neurons in Alzheimer's disease (AD). However, its delivery to the brain remains a challenge. Herein, NGF is loaded into degradable oxidized porous silicon (PSiO2 ) carriers, which are designed to carry and continuously release the protein over a 1 month period. The released NGF exhibits a substantial neuroprotective effect in differentiated rat pheochromocytoma PC12 cells against amyloid-beta (Aß)-induced cytotoxicity, which is associated with Alzheimer's disease. Next, two potential localized administration routes of the porous carriers into murine brain are investigated: implantation of PSiO2 chips above the dura mater, and biolistic bombardment of PSiO2 microparticles through an opening in the skull using a pneumatic gene gun. The PSiO2 -implanted mice are monitored for a period of 8 weeks and no inflammation or adverse effects are observed. Subsequently, a successful biolistic delivery of these highly porous microparticles into a live-mouse brain is demonstrated for the first time. The bombarded microparticles are observed to penetrate the brain and reach a depth of 150 µm. These results pave the way for using degradable PSiO2 carriers as potential localized delivery systems for NGF to the brain.

Distinct Effects of O-GlcNAcylation and Phosphorylation of a Tau-Derived Amyloid Peptide on Aggregation of the Native Peptide.

Protein phosphorylation and O-GlcNAcylation are very common nucleoplasmic post-translational modifications. Mono-addition of either the phosphate or the O-GlcNAc group were shown to inhibit the self-aggregation of amyloidogenic proteins and peptides, which is the hallmark of various protein misfolding diseases. However, their comparable effect upon co-incubation with a native non-modified amyloid scaffold has not been reported. O-linked glycans and phosphate variants of the tau protein-derived VQIVYK hexapeptide motif were generated as a simplified amyloid scaffold model and demonstrate that, while self-aggregation can be attenuated by either a single glycan or a phosphate unit, only co-incubation with the O-GlcNAc variant inhibits aggregation of the native peptide. These results shed light on the role of post-translational modifications in protein aggregation and suggest a novel therapeutic approach to protein misfolding diseases.

Selective Inhibition of Aggregation and Toxicity of a Tau-Derived Peptide using Its Glycosylated Analogues.

Protein glycosylation is a ubiquitous post-translational modification that regulates the folding and function of many proteins. Misfolding of protein monomers and their toxic aggregation are the hallmark of many prevalent diseases. Thus, understanding the role of glycans in protein aggregation is highly important and could contribute both to unraveling the pathology of protein misfolding diseases as well as providing a means for modifying their course for therapeutic purposes. Using ß-O-linked glycosylated variants of the highly studied Tau-derived hexapeptide motif VQIVYK, which served as a simplified amyloid model, we demonstrate that amyloid formation and toxicity can be strongly attenuated by a glycan unit, depending on the nature of the glycan itself. Importantly, we show for the first time that not only do glycans hinder self-aggregation, but the glycosylated peptides are capable of inhibiting aggregation of the non-modified corresponding amyloid scaffold.

Self-Assembled Cyclic d,l-α-Peptides as Generic Conformational Inhibitors of the α-Synuclein Aggregation and Toxicity: In Vitro and Mechanistic Studies.

Many peptides and proteins with large sequences and structural differences self-assemble into disease-causing amyloids that share very similar biochemical and biophysical characteristics, which may contribute to their cross-interaction. Here, we demonstrate how the self-assembled, cyclic d,l-α-peptide CP-2, which has similar structural and functional properties to those of amyloids, acts as a generic inhibitor of the Parkinson's disease associated α-synuclein (α-syn) aggregation to toxic oligomers by an "off-pathway" mechanism. We show that CP-2 interacts with the N-terminal and the non-amyloid-ß component region of α-syn, which are responsible for α-syn's membrane intercalation and self-assembly, thus changing the overall conformation of α-syn. CP-2 also remodels α-syn fibrils to nontoxic amorphous species and permeates cells through endosomes/lysosomes to reduce the accumulation and toxicity of intracellular α-syn in neuronal cells overexpressing α-syn. Our studies suggest that targeting the common structural conformation of amyloids may be a promising approach for developing new therapeutics for amyloidogenic diseases.

Sonochemically-Produced Metal-Containing Polydopamine Nanoparticles and Their Antibacterial and Antibiofilm Activity.

A facile one-pot sonochemical synthesis of Cu-, Ag-, and hybrid Cu/Ag-based polydopamine nanoparticles (Cu-, Ag-, and Cu/Ag-PDA-NPs) and the mechanisms by which they exert antibacterial and antibiofilm activities are reported. We showed that the nanoparticles are spherical with a core-shell structure. Whereas Cu is chelated to the shell of Cu-PDA-NPs in oxidation states of +1/+2, the core of Ag-PDA-NPs is filled with elemental Ag°. Sonochemical irradiation of dopamine in the presence of both Cu(2+) and Ag(+) generates hybrid Cu/Ag-PDA-NPs, whose shells are composed of Cu-chelated PDA with Ag° in the core. The redox potential of the metals was found to be the main determinant of the location and oxidation state of the metals. Leaching studies under physiological conditions reveal a relatively fast release of Cu ions from the shell, whereas Ag leaches very slowly from the core. The metal-containing PDA-NPs are highly microbicidal and exhibit potent antibiofilm activity. The combination of both metals in Cu/Ag-PDA-NPs is especially effective against bacteria and robust biofilms, owing to the dual bactericidal mechanisms of the metals. Most importantly, both Ag- and Cu/Ag-PDA-NPs proved to be significantly more antibacterial than commercial Ag-NPs while exhibiting lower toxicity toward NIH 3T3 mouse embryonic fibroblasts. Mechanistically, the metal-containing PDA-NPs generate stable PDA-semiquinone and reactive oxygen species under physiological conditions, which contribute at least partly to the antimicrobial activity. We also demonstrated that simple treatment of surfaces with Ag-PDA-NPs converts them to antibacterial, the activity of which was preserved even after prolonged storage under ambient conditions.

Antibacterial and antibiofilm surfaces through polydopamine-assisted immobilization of lysostaphin as an antibacterial enzyme.

Antibiotic resistance and the colonization of bacteria on surfaces, often as biofilms, prolong hospitalization periods, increase mortality, and are thus major concerns for health care providers. There is an urgent need for antimicrobial and antibiofilm surface treatments that are permanent, can eradicate both biofilms and planktonic pathogens over long periods of time, and do not select for resistant strains. In this study, we have demonstrated a simple, robust, and biocompatible method that utilizes the adhesive property of polydopamine (PDA) to covalently attach the antimicrobial enzyme lysostaphin (Lst) to a variety of surfaces to generate antibacterial and antibiofilm interfaces. The immobilization of the recombinant Lst onto PDA-coated surfaces was carried out under physiological conditions, most probably through the C-terminal His6-tag fragment of the enzyme, minimizing the losses of bioagent activity. The modified surfaces were extensively characterized by X-ray photoelectron spectroscopy and peak force quantitative nanomechanical mapping (PeakForce QNM) AFM-based method, and the presence of Lst on the surfaces was further confirmed immunochemically using anti-Lst antibody. We also found that, in contrast to the physically adsorbed Lst, the covalently attached Lst does not leach from the surfaces and maintains its endopeptidase activity to degrade the staphylococcal cell wall, avoiding most intracellular bacterial resistance mechanisms. Moreover, the Lst-coated surfaces kill hospital strains of Staphylococcus aureus in less than 15 min and prevent biofilm formation. This immobilization method should be applicable also to other proteins and enzymes that are recombinantly expressed to include the His6-tag fragment.

Tubular cell phenotype in HIV-associated nephropathy: role of phospholipid lysophosphatidic acid.

Collapsing glomerulopathy and microcysts are characteristic histological features of HIV-associated nephropathy (HIVAN). We have previously reported the role of epithelial mesenchymal transition (EMT) in the development of glomerular and tubular cell phenotypes in HIVAN. Since persistent tubular cell activation of NFκB has been reported in HIVAN, we now hypothesize that HIV may be contributing to tubular cell phenotype via lysophosphatidic acid (LPA) mediated downstream signaling. Interestingly, LPA and its receptors have also been implicated in the tubular interstitial cell fibrosis (TIF) and cyst formation in autosomal dominant polycystic kidney disease (PKD). Primary human proximal tubular cells (HRPTCs) were transduced with either empty vector (EV/HRPTCs), HIV (HIV/HRPTCs) or treated with LPA (LPA/HRPTC). Immunoelectrophoresis of HIV/HRPTCs and LPA/HRPTCs displayed enhanced expression of pro-fibrotic markers: a) fibronectin (2.25 fold), b) connective tissue growth factor (CTGF; 4.8 fold), c) α-smooth muscle actin (α-SMA; 12 fold), and d) collagen I (5.7 fold). HIV enhanced tubular cell phosphorylation of ILK-1, FAK, PI3K, Akt, ERKs and P38 MAPK. HIV increased tubular cell transcriptional binding activity of NF-κB; whereas, a LPA biosynthesis inhibitor (AACOCF3), a DAG kinase inhibitor, a LPA receptor blocker (Ki16425), a NF-κB inhibitor (PDTC) and NFκB-siRNA not only displayed downregulation of a NFκB activity but also showed attenuated expression of profibrotic/EMT genes in HIV milieu. These findings suggest that LPA could be contributing to HIV-induced tubular cell phenotype via NFκB activation in HIVAN.

In vitro and mechanistic studies of an antiamyloidogenic self-assembled cyclic D,L-α-peptide architecture.

Misfolding of the Aß protein and its subsequent aggregation into toxic oligomers are related to Alzheimer's disease. Although peptides of various sequences can self-assemble into amyloid structures, these structures share common three-dimensional features that may promote their cross-reaction. Given the significant similarities between amyloids and the architecture of self-assembled cyclic D,L-α-peptide, we hypothesized that the latter may bind and stabilize a nontoxic form of Aß, thereby preventing its aggregation into toxic forms. By screening a focused library of six-residue cyclic D,L-α-peptides and optimizing the activity of a lead peptide, we found one cyclic D,L-α-peptide (CP-2) that interacts strongly with Aß and inhibits its aggregation. In transmission electron microscopy, optimized thioflavin T and cell survival assays, CP-2 inhibits the formation of Aß aggregates, entirely disassembles preformed aggregated and fibrillar Aß, and protects rat pheochromocytoma PC12 cells from Aß toxicity, without inducing any toxicity by itself. Using various immunoassays, circular dichroism spectroscopy, photoinduced cross-linking of unmodified proteins (PICUP) combined with SDS/PAGE, and NMR, we probed the mechanisms underlying CP-2's antiamyloidogenic activity. NMR spectroscopy indicates that CP-2 interacts with Aß through its self-assembled conformation and induces weak secondary structure in Aß. Upon coincubation, CP-2 changes the aggregation pathway of Aß and alters its oligomer distribution by stabilizing small oligomers (1-3 mers). Our results support studies suggesting that toxic early oligomeric states of Aß may be composed of antiparallel ß-peptide structures and that the interaction of Aß with CP-2 promotes formation of more benign parallel ß-structures. Further studies will show whether these kinds of abiotic cyclic D,L-α-peptides are also beneficial as an intervention in related in vivo models.

Effective targeting of Aß to macrophages by sonochemically prepared surface-modified protein microspheres.

Imbalanced homeostasis and oligomerization of the amyloid-ß (Aß) peptide in the brain are hallmarks of Alzheimer's disease (AD). Microglia and macrophages play a critical role in the etiology of AD either by clearing Aß from the brain or inducing inflammation. Recent evidence suggests that clearance of Aß by microglia/macrophages via the phagocytic pathway is defective in AD, which can contribute to the accumulation of Aß in the brain. We have recently demonstrated that protein microspheres modified at their surface with multiple copies of an Aß-recognition motif can strongly bind Aß, inhibit its aggregation, and directly reduce its toxicity by sequestering it from the medium. Here, we describe how microsphere-bound Aß can stimulate microglial cells and be phagocytosed through a mechanism that is distinct from that of Aß removal and, thus, contribute to the clearance of Aß, even by defective microglial cells. The phagocytosis was most effective, with microspheres having a diameter of <1 µm. The introduction of polyethylene glycol to the surface of the microspheres changed the kinetics of the phagocytosis. Moreover, while aggregated Aß induced a significant inflammatory response that was manifested by the release of TNF-α, the microsphere-bound Aß dramatically reduced the amount of cytokine released from microglial cells.

Aza-Residue Modulation of Cyclic d,l-α-Peptide Nanotube Assembly with Enhanced Anti-Amyloidogenic Activity.

Transient soluble oligomers of amyloid-ß (Aß) are considered among the most toxic species in Alzheimer's disease (AD). Soluble Aß oligomers accumulate early prior to insoluble plaque formation and cognitive impairment. The cyclic d,l-α-peptide CP-2 (1) self-assembles into nanotubes and demonstrates promising anti-amyloidogenic activity likely by a mechanism involving engagement of soluble oligomers. Systematic replacement of the residues in peptide 1 with aza-amino acid counterparts was performed to explore the effects of hydrogen bonding on propensity to mitigate Aß aggregation and toxicity. Certain azapeptides exhibited improved ability to engage, alter the secondary structure, and inhibit aggregation of Aß. Moreover, certain azapeptides disassembled preformed Aß fibrils and protected cells from Aß-mediated toxicity. Substitution of the l-norleucine3 and d-serine6 residues in peptide 1 with aza-norleucine and aza-homoserine provided, respectively, nontoxic [azaNle3]-1 (4) and [azaHse6]-1 (7), that significantly abated symptoms in a transgenic Caenorhabditis elegans AD model by decreasing Aß oligomer levels.

Noninvasive Treatment of Alzheimer's Disease with Scintillating Nanotubes.

Effective and accessible treatments for Alzheimer's disease (AD) are urgently needed. Soluble Aß oligomers are identified as neurotoxic species in AD and targeted in antibody-based drug development to mitigate cognitive decline. However, controversy exists concerning their efficacy and safety. In this study, an alternative strategy is proposed to inhibit the formation of Aß oligomers by selectively oxidizing specific amino acids in the Aß sequence, thereby preventing its aggregation. Targeted oxidation is achieved using biocompatible and blood-brain barrier-permeable multicomponent nanoscintillators that generate singlet oxygen upon X-ray interaction. Surface-modified scintillators interact selectively with Aß and, upon X-ray irradiation, inhibit the formation of neurotoxic aggregates both in vitro and in vivo. Feeding transgenic Caenorhabditis elegans expressing human Aß with the nanoscintillators and subsequent irradiation with soft X-ray reduces Aß oligomer levels, extends lifespan, and restores memory and behavioral deficits. These findings support the potential of X-ray-based therapy for AD and warrant further development.

Surface-modified protein microspheres capture amyloid-ß and inhibit its aggregation and toxicity.

The biocompatible and biodegradable properties of protein microspheres and the recent advances in their preparation have generated considerable interest of utilizing these core-shell structures for drug delivery and diagnostic applications. However, effective targeting of protein microspheres to desirable cells or loci still remains a challenge. Here, we describe for the first time a facile one-pot sonochemical approach for covalent modification of protein microspheres made from serum albumin; the surface of which is covalently decorated with a short recognition peptide to target amyloid-ß (Aß) as the main pathogenic protein in Alzheimer's disease (AD). The microspheres were characterized for their morphology, size, and entrapment efficacy by electron microscopy, dynamic light scattering and confocal microscopy. Fluorescence-activated cell-sorting analysis and Thioflavin-T binding assay demonstrated that the conjugated microspheres bind with high affinity and selectivity to Aß, sequester it from the medium and reduce its aggregation. Upon incubation with Aß, the microspheres induced formation of amorphous aggregates on their surface with no apparent fibrillar structure. Moreover, the microspheres directly reduced the Aß-induced toxicity toward neuron like PC12 cells. The conjugated microspheres are smaller than unmodified microspheres and remained stable throughout the incubation under physiological conditions.

The neuropeptides GnRH-II and GnRH-I are produced by human T cells and trigger laminin receptor gene expression, adhesion, chemotaxis and homing to specific organs.

Can T cells be directly activated to de novo gene expression by gonadotropin-releasing hormone-II (GnRH-II), a unique 10-amino-acid neuropeptide conserved through 500 million years of evolution? GnRH-II, which has been identified in mammals, shares 70% homology with the mammalian hypothalamic neurohormone GnRH (GnRH-I), the primary regulator of reproduction, but is encoded by a different gene. Although both neuropeptides are produced mainly in brain, their localization and promoter regulation differ, suggestive of distinct functions. Indeed, GnRH-II barely affects reproduction and its role in mammalian physiology is unknown. We find here that human normal and leukemic T cells produce GnRH-II and GnRH-I. Further, exposure of normal or cancerous human or mouse T cells to GnRH-II or GnRH-I triggered de novo gene transcription and cell-surface expression of a 67-kD non-integrin laminin receptor that is involved in cellular adhesion and migration and in tumor invasion and metastasis. GnRH-II or GnRH-I also induced adhesion to laminin and chemotaxis toward SDF-1alpha, and augmented entry in vivo of metastatic T-lymphoma into the spleen and bone marrow. Homing of normal T cells into specific organs was reduced in mice lacking GnRH-I. A specific GnRH-I-receptor antagonist blocked GnRH-I- but not GnRH-II-induced effects, which is suggestive of signaling through distinct receptors. We suggest that GnRH-II and GnRH-I, secreted from nerves or autocrine or paracrine sources, interact directly with T cells and trigger gene transcription, adhesion, chemotaxis and homing to specific organs, which may be of clinical relevance.

Glucose-Functionalized Liposomes for Reducing False Positives in Cancer Diagnosis.

Fluorodeoxyglucose-positron emission tomography (18F-FDG-PET) is a powerful tool for cancer detection, staging, and follow-up. However, 18F-FDG-PET imaging has high rates of false positives, as it cannot distinguish between tumor and inflammation regions that both feature increased glucose metabolic activity. In the present study, we engineered liposomes coated with glucose and the chelator dodecane tetraacetic acid (DOTA) complexed with copper, to serve as a diagnostic technology for differentiating between cancer and inflammation. This liposome technology is based on FDA-approved materials and enables complexation with metal cations and radionuclides. We found that these liposomes were preferentially uptaken by cancer cell lines with high metabolic activity, mediated via glucose transporter-1. In vivo, these liposomes were avidly uptaken by tumors, as compared to liposomes without glucose coating. Moreover, in a combined tumor-inflammation mouse model, these liposomes accumulated in the tumor tissue and not in the inflammation region. Thus, this technology shows high specificity for tumors while evading inflammation and has potential for rapid translation to the clinic and integration with existing PET imaging systems, for effective reduction of false positives in cancer diagnosis.

One-step preparation of multifunctional chitosan microspheres by a simple sonochemical method.

Chitosan is a biodegradable natural polymer with great potential for pharmaceutical applications due to its biocompatibility, high charge density, nontoxicity, and mucoadhesion properties. Processing techniques for the preparation of chitosan microspheres have been extensively developed since the 1980s. The present paper describes for the first time a fast and one-step process for the preparation of stable chitosan microspheres by a simple sonochemical method. The microspheres were characterized by their particle size, surface morphology, stability, and drug-entrapment efficiency. The average size of the microspheres was found to be around 1 mum with a narrow size distribution, which enabled them to be used for in vivo applications. The encapsulation of different dyes into these microspheres was readily achieved with more than 75 % efficacy by dissolving them into the organic phase before sonication. The chitosan microspheres demonstrated excellent stability toward acidic and basic conditions ranging from pH 4 to 9, thereby indicating their implementation as possible therapeutic and diagnostic agents. The stability of these microspheres appears to be contributed from intermolecular imine cross-linking in addition to other noncovalent interactions. The ability of the surface-exposed amino groups of chitosan microspheres to undergo chemical conjugation with potential drugs and/or targeting vectors was determined by their reaction with fluorescein isothiocyanate (FITC) and fluorescamine followed by confocal microscopy.

Bifunctional Carbon Dots-Magnetic and Fluorescent Hybrid Nanoparticles for Diagnostic Applications.

There is a huge demand for materials capable of simple detection or separation after conjugation with specific biologic substances when applied as a diagnostic tools. Taking into account the photoluminescence properties of C-dots and the highly magnetic properties of Fe(0), a new hybrid composite of these components was synthesized via ultrasound irradiation. The material was fully characterized by various physicochemical techniques. The main goal of the current study was to obtain a highly magnetic and intense fluorescent hybrid material. The goal was achieved. In addition, magnetic particles tended to agglomerate. The new hybrid can be suspended in ethanol, which is an additional feature of the current research. The dispersion of the hybrid nanoparticles in ethanol was achieved by utilizing the interaction of iron particles with C-dots which were decorated with functional groups on their surface. The newly formed hybrid material has potential applications in diagnostic by conjugating with specific antibodies or with any other biologic compounds. Such application may be useful in detection of various diseases such as: cancer, tuberculosis, etc.

Antibacterial cyclic D,L-alpha-glycopeptides.

We report the design, synthesis, membrane activity, biophysical characterization, and in vitro antibacterial activities of cationic cyclic D,L-alpha-glycopeptides bearing d-glucosamine (GlcNH(2)), D-galactose (Gal), or D-mannose (Man) glycosyl side chains.