1,2-Mannobioside mimic: synthesis, DC-SIGN interaction by NMR and docking, and antiviral activity

The design and preparation of carbohydrate ligands for DC-SIGN is a topic of high interest because of the role played by this C-type lectin in immunity and infection processes. The low chemical stability of carbohydrates against enzymatic hydrolysis by glycosylases has stimulated the search for new alternatives more stable in vivo. Herein, we present a good alternative for a DC-SIGN ligand based on a mannobioside mimic with a higher enzymatic stability than the corresponding disaccharide. NMR and docking studies have been performed to study the interaction of this mimic with DC-SIGN in solution demonstrating that this pseudomannobioside is a good ligand for this lectin. In vitro studies using an infection model with Ebola pseudotyped virus demonstrates that this compound presents an antiviral activity even better than the corresponding disaccharide and could be an interesting ligand to prepare multivalent systems with higher affinities for DC-SIGN with potential biomedical applications.     

Human Milk Oligosaccharide 2′-Fucosyllactose Inhibits Ligand Binding to C-Type Lectin DC-SIGN but Not to Langerin

Human milk oligosaccharides (HMOs) and their most abundant component, 2′-Fucosyllactose (2′-FL), are known to be immunomodulatory. Previously, it was shown that HMOs and 2′-FL bind to the C-type lectin receptor DC-SIGN. Here we show, using a ligand-receptor competition assay, that a whole mixture of HMOs from pooled human milk (HMOS) and 2′-FL inhibit the binding of the carbohydrate-binding receptor DC-SIGN to its prototypical ligands, fucose and the oligosaccharide Lewis-B, (Le^b) in a dose-dependent way. Interestingly, such inhibition by HMOS and 2′-FL was not detected for another C-type lectin, langerin, which is evolutionarily similar to DC-SIGN. The cell-ligand competition assay using DC-SIGN expressing cells confirmed that 2′-FL inhibits the binding of DC-SIGN to Le^b. Molecular dynamic (MD) simulations show that 2′-FL exists in a preorganized bioactive conformation before binding to DC-SIGN and this conformation is retained after binding to DC-SIGN. Le^b has more flexible conformations and utilizes two binding modes, which operate one at a time via its two fucoses to bind to DC-SIGN. Our hypothesis is that 2′-FL may have a reduced entropic penalty due to its preorganized state, compared to Le^b, and it has a lower binding enthalpy, suggesting a better binding to DC-SIGN. Thus, due to the better binding to DC-SIGN, 2′-FL may replace Le^b from its binding pocket in DC-SIGN. The MD simulations also showed that 2′-FL does not bind to langerin. Our studies confirm 2′-FL as a specific ligand for DC-SIGN and suggest that 2′-FL can replace other DC-SIGN ligands from its binding pocket during the ligand-receptor interactions in possible immunomodulatory processes.     

Comparative analysis reveals selective recognition of glycans by the dendritic cell receptors DC-SIGN and Langerin

DC-SIGN (dendritic cell-specific ICAM-3 grabbing non-integrin) and Langerin are homologous C-type lectins expressed as cell-surface receptors on different populations of dendritic cells (DCs). DC-SIGN interacts with glycan structures on HIV-1, facilitating virus survival, transmission and infection, whereas Langerin, which is characteristic of Langerhans cells (LCs), promotes HIV-1 uptake and degradation. Here we describe a comprehensive comparison of the glycan specificities of both proteins by probing a synthetic carbohydrate microarray comprising 275 sugar compounds using the bacterially produced and fluorescence-labeled, monomeric carbohydrate-recognition domains (CRDs) of DC-SIGN and Langerin. In this side-by-side study DC-SIGN was found to preferentially bind internal mannose residues of high-mannose-type saccharides and the fucose-containing blood-type antigens H, A, B, Le(a), Le(b) Le(x), Le(y), sialyl-Le(a) as well as sulfatated derivatives of Le(a) and Le(x). In contrast, Langerin appeared to recognize a different spectrum of compounds, especially those containing terminal mannose, terminal N-acetylglucosamine and 6-sulfogalactose residues, but also the blood-type antigens H, A and B. Of the Lewis antigens, only Le(b), Le(y), sialyl-Le(a) and the sialyl-Le(x) derivative with 6'-sulfatation at the galactose (sialyl-6SGal Le(x)) were weakly bound by Langerin. Notably, Ca(2+)-independent glycan-binding activity of Langerin could not be detected either by probing the glycan array or by isothermal titration calorimetry of the CRD with mannose and mannobiose. The precise knowledge of carbohydrate specificity of DC-SIGN and Langerin receptors resulting from our study may aid the future design of microbicides that specifically affect the DC-SIGN/HIV-1 interaction while not compromising the protective function of Langerin.     

Identification of Important N-Linked Glycosylation Sites in the Hemagglutinin Protein and Their Functional Impact on DC-SIGN Mediated Avian Influenza H5N1 Infection

DC-SIGN, a C-type lectin mainly expressed in dendritic cells (DCs), has been reported to mediate several viral infections. We previously reported that DC-SIGN mediated H5N1 influenza A virus (AIVs) infection, however, the important DC-SIGN interaction with N-glycosylation sites remain unknown. This study aims to identify the optimal DC-SIGN interacting N-glycosylation sites in HA proteins of H5N1-AIVs. Results from NetNGlyc program analyzed the H5 hemagglutinin sequences of isolates during 2004–2020, revealing that seven and two conserved N-glycosylation sites were detected in HA1 and HA2 domain, respectively. A lentivirus pseudotyped A/Vietnam/1203/04 H5N1 envelope (H5N1-PVs) was generated which displayed an abundance of HA5 proteins on the virions via immuno-electron microscope observation. Further, H5N1-PVs or reverse-genetics (H5N1-RG) strains carrying a serial N-glycosylated mutation was generated by site-directed mutagenesis assay. Human recombinant DC-SIGN (rDC-SIGN) coated ELISA showed that H5N1-PVs bound to DC-SIGN, however, mutation on the N27Q, N39Q, and N181Q significantly reduced this binding (p < 0.05). Infectivity and capture assay demonstrated that N27Q and N39Q mutations significantly ameliorated DC-SIGN mediated H5N1 infection. Furthermore, combined mutations (N27Q&N39Q) significantly waned the interaction on either H5N1-PVs or -RG infection in cis and in trans (p < 0.01). This study concludes that N27 and N39 are two essential N-glycosylation contributing to DC-SIGN mediating H5N1 infection.     

Enterotoxigenic <Emphasis Type="Italic">Escherichia coli</Emphasis> strains bind bovine milk gangliosides in a ceramide-dependent process

Diarrhea caused by enterotoxigenic Escherichia coli (ETEC) is the main infectious disease of newborn calves. The first step of infection involves bacterial attachment to the intestinal mucosa. This adhesion is mediated by fimbriae that recognize some glycoconjugates on the host cell surface, in particular, several gangliosides. Because milk also contains gangliosides, these have been suggested to serve as ligands for bacterial fimbriae and thus prevent the bacterial attachment to mucosa. The most relevant ETEC strains in calves, including those with K99 and F41 fimbriae, were assayed to determine whether they are able to bind gangliosides isolated from several stages of bovine lactation. Both GM3 and GD3, the main gangliosides of milk, were recognized by ETEC strains, although the different fimbriae showed diverse levels of affinity. Unexpectedly, the adhesion to colostral gangliosides was considerably weaker than that to gangliosides from the other stages of lactation. Because the carbohydrate moiety did not change and because differences in the percentages of unsaturated FA and sphingosine between colostrum and other stages were observed, we conclude that the differences in adhesion could be due to a different composition of the ganglioside caramide.     

Poly(amidoamine) dendritic structures,bearing different end groups,as adhesion promoters for urea–formaldehyde wood adhesive system

A series of core‐shell poly(amidoamine) (PAMAM) dendritic compounds bearing different end groups such as  OH, NH₂, and NH₃⁺⁻Cl up to the third generation were prepared via successive Michael addition of a nucleophilic core (ethylenediamine) to methylacrylate followed by amination steps using ethylenediamine for the amine‐terminated while ethanolamine for the hydroxyl‐terminated compounds, also the protonated ammonium salt terminated form was obtained by cationization of the amine‐terminated form using hydrochloric acid solution. The Surface activity and aggregation behavior of the corresponding aqueous solutions of the prepared generations with their different end groups were studied and confirmed by surface tension measurements using ring method technique. The prepared dendrimers showed high surface activity and the measurements revealed their ability to self aggregate in water at very low concentrations, critical aggregation concentrations (CACs). The CACs were found to decrease with increasing the generation number, which implies that molecular weight and structure play important rules in controlling the surface activity and CAC. The dendritic compounds proved to be effective as adhesion promoters for urea formaldehyde (UF) resins when applied as wood adhesive systems, which was ascribed in partial to the improved wetting over the substrate, a role that is fundamentally related to the huge number of function groups present at the interface. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2011     

Transfection of Vitamin D3-Induced Tolerogenic Dendritic Cells for the Silencing of Potential Tolerogenic Genes. Identification of CSF1R-CSF1 Signaling as a Glycolytic Regulator

The use of autologous tolerogenic dendritic cells (tolDC) has become a promising strategy to re-establish immune tolerance in autoimmune diseases. Among the different strategies available, the use of vitamin D3 for the generation of tolDC (VitD3-tolDC) has been widely tested because of their immune regulatory properties. To identify molecules and pathways involved in the generation of VitD3-tolDC, we established an easy and fast gene silencing method based on the use of Viromer blue to introduce siRNA into monocytes on day 1 of culture differentiation. The analysis of the effect of CD209 (DC-SIGN) and CD115 (CSF1R) down-modulation on the phenotype and functionality of transfected VitD3-tolDC revealed a partial role of CD115 in their tolerogenicity. Further investigations showed that CSF1R-CSF1 signaling is involved in the induction of cell metabolic reprogramming, triggering glycolysis to produce high amounts of lactate, a novel suppressive mechanism of T cell proliferation, recently found in autologous tolerogenic dendritic cells (ATDCs).     

Biological Evaluation of Multivalent Lewis X–MGL‐1 Interactions

Myeloid C‐type lectin receptors (CLRs) expressed by antigen‐presenting cells are pattern‐recognition receptors involved in the recognition of pathogens as well as of self‐antigens. The interaction of carbohydrate ligands with a CLR can trigger immune responses. Although several CLR ligands are known, there is limited insight into CLR targeting by carbohydrate ligands. The weak affinity of lectin–carbohydrate interactions often renders multivalent carbohydrate presentation necessary. Here, we have analyzed the impact of multivalent presentation of the trisaccharide Lewis X (Le^X) epitope on its interaction with the CLR macrophage galactose‐type lectin‐1 (MGL‐1). Glycan arrays, including N‐glycan structures with terminal Le^X, were prepared by enzymatic extension of immobilized synthetic core structures with two recombinant glycosyltransferases. Incubation of arrays with an MGL‐1‐hFc fusion protein showed up to tenfold increased binding to multiantennary N‐glycans displaying Le^X structures, compared to monovalent Le^X trisaccharide. Multivalent presentation of Le^X on the model antigen ovalbumin (OVA) led to increased cytokine production in a dendritic cell /T cell coculture system. Furthermore, immunization of mice with Le^X‐OVA conjugates modulated cytokine production and the humoral response, compared to OVA alone. This study provides insights into how multivalent carbohydrate–lectin interactions can be exploited to modulate immune responses.     

Metallo-functionalized first-generation salicylaldimine poly(propylenimine) tetraamine dendrimers: Electrochemical study and atomic force microscopy imaging

The adsorption and the redox processes of two first-generation salicylaldiamine dendritic ligands and their copper, cobalt and nickel metallo-functionalized complexes have been studied at two types of carbon electrode surface. Glassy carbon (GC) was used in an electrochemistry study and highly oriented pyrolitic graphite (HOPG) in ex situ atomic force microscopy (AFM) imaging. All salicylaldimine ligands and their metallo-functionalized complexes adsorb on the surface of the HOPG electrode, resulting in the formation of nanoclusters and films, which vary between 0.9 and 6 nm in size, depending on the metallo-functionalized salicylaldimine dendrimer chemical composition and solution concentration. Differential pulse voltammetry of the surface-confined films has shown that the anodic reactions observed correspond to the oxidation of the hydroxyl groups present in the ligand structure of all compounds. However, by following the changes in peak currents, potentials and width at half height it has been shown that destabilization of the ligand internal structure occurred in the metallo-functionalized complexes depending on the metal involved. The electrochemical behaviour of the surface-confined films observed in buffer solution was related to the morphology, obtained by AFM, of the immobilised first-generation salicylaldiamine dendritic ligands and corresponding salicylaldimine metallo-functionalized complexes.     

Air‐Stable and Highly Active Dendritic Phosphine Oxide‐ Stabilized Palladium Nanoparticles: Preparation,Characterization and Applications in the Carbon‐Carbon Bond Formation and Hydrogenation Reactions

Dendrimer‐stabilized palladium nanoparticles were formed in the reduction of palldium bis(acetylacetonate) [Pd(acac)₂] in the presence of phosphine dendrimer ligands using hydrogen in tetrahydrofuran. The resulting Pd nanoparticles were characterized by TEM, ³¹P NMR and ³¹P MAS NMR. The results indicated that the dendritic phosphine ligands were oxidized to phosphine oxides. These dendrimer‐stabilized Pd nanoparticles were demonstrated to be efficient catalysts for Suzuki and Stille coupling reactions and hydrogenations. The dendritic wedges served as a stabilizer for keeping the nanoparticles from aggregating, and as a vehicle for facilitating the separation and/or the recycling of the Pd catalyst. In the case of the Suzuki coupling reaction, these Pd nanoparticles exhibited high catalytic efficiency (TON up to 65,000) and air stability as compared with the commonly used homogeneous catalyst tetrakis(triphenylphosphine)palladium [Pd(PPh₃)₄]. In addition, the results obtained from the bulky dendritic substrate suggest that the Pd nanoparticles might act as reservoir of catalytically active species, and that the reaction is actually catalyzed by the soluble Pd(0) and/or Pd(II) species leached from the nanoparticle surface.     

Implication of scavenger receptors in the interactions between diesel exhaust particles and immature or mature dendritic cells

Background  

The exposure to pollutants such as diesel exhaust particles (DEP) is associated with an increased incidence of respiratory diseases. However, the mechanisms by which DEP have an effect on human health are not completely understood. In addition to their action on macrophages and airway epithelial cells, DEP also modulate the functions of dendritic cells (DC). These professional antigen-presenting cells are able to discriminate unmodified self from non-self thanks to pattern recognition receptors such as the Toll like Receptors (TLR) and Scavenger Receptors (SR). SR were originally identified by their ability to bind and internalize modified lipoproteins and microorganisms but also particles and TLR agonists. In this study, we assessed the implication of SR in the effects of DEP associated or not with TLR agonists on monocyte-derived DC (MDDC). For this, we studied the regulation of CD36, CXCL16, LOX-1, SR-A1 and SR-B1 expression on MDDC treated with DEP associated or not with TLR2, 3 and 4 ligands. Then, the capacity of SR ligands (dextran sulfate and maleylated-ovalbumin) to block the effects of DEP on the function of lipopolysaccharide (LPS)-activated DC has been evaluated.     

Synthesis of organic–inorganic hybrid polymeric nanocomposites for the hard coat application

An organic–inorganic hybrid polymeric nanocomposite has been synthesized for making UV‐curable hard coats. This nanocomposite consists of nano‐sized colloidal silica functionalized with vinyltriethoxysilane (VTES) and dendritic acrylic oligomers (DAO) which have been formed earlier via a reaction of ethylenediamine (EDA) with trimethylopropane triacrylate (TMPTA). Applied as a hard coat on top of a polyethylene terephthalate (PET) film, this nanocomposite has a short UV‐cure time and the cured coat has an enhanced thermal decomposition temperature (T_d), 89–90% transparency, increased hardness up to 3H, better adhesion up to 4B, and a flat surface with a root mean square roughness of 2–4 nm. The preparation as well as the characterization of the constituting species and the final hybrid are described in detail. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 103: 3985–3993, 2007     

Synthesis of well‐defined dendritic hyperbranched polymers by iterative methodologies using living/controlled polymerizations

This review presents firstly the synthesis of various dendritic hyperbranched polymers with well‐defined structures by generation‐based growth methodologies using living/controlled polymerization. Secondly, the synthesis of dendritic hyperbranched poly(methyl methacrylate)s (PMMAs) and their functionalized block copolymers using a novel iterative methodology is described. The methodology involves a two‐reaction sequence in each iterative process: (a) a linking reaction of α‐functionalized living anionic PMMA with tert‐butyldimethylsilyloxymethylphenyl (SMP) groups with benzyl bromide (BnBr)‐chain‐end‐functionalized polymer and (b) a transformation reaction of the SMP groups into BnBr functions. This reaction sequence is repeated several times to construct high‐generation (maximum seventh generation) dendritic hyperbranched polymers. Similar branched architectural block copolymers have also been synthesized by the same iterative methodology using other α‐functionalized living anionic polymers. Surface structures of the resulting dendritic hyperbranched block copolymers composed of PMMA and poly(2‐(perfluorobutyl)ethyl methacrylate) segments have been characterized using X‐ray photoelectron spectroscopy and contact angle measurements. Solution behaviors of dendritic hyperbranched PMMAs with different generations and branch densities are discussed based on their intrinsic viscosities, g′ values and R_h values. Copyright © 2007 Society of Chemical Industry     

Modularly designed transition metal PNP and PCP pincer complexes based on aminophosphines: synthesis and catalytic applications

Transition metal complexes are indispensable tools for any synthetic chemist. Ideally, any metal-mediated process should be fast, clean, efficient, and selective and take place in a catalytic manner. These criteria are especially important considering that many of the transition metals employed in catalysis are rare and expensive. One of the ways of modifying and controlling the properties of transition metal complexes is the use of appropriate ligand systems, such as pincer ligands. Usually consisting of a central aromatic backbone tethered to two two-electron donor groups by different spacers, this class of tridentate ligands have found numerous applications in various areas of chemistry, including catalysis, due to their combination of stability, activity, and variability. As we focused on pincer ligands featuring phosphines as donor groups, the lack of a general method for the preparation of both neutral (PNP) and anionic (PCP) pincer ligands using similar precursor compounds as well as the difficulty of introducing chirality into the structure of pincer ligands prompted us to investigate the use of amines as spacers between the aromatic ring and the phosphines. By introduction of aminophosphine and phosphoramidite moieties into their structure, the synthesis of both PNP and PCP ligands can be achieved via condensation reactions between aromatic diamines and electrophilic chlorophosphines (or chlorophosphites). Moreover, chiral pincer complexes can be easily obtained by using building blocks obtained from the chiral pool. Thus, we have developed a modular synthetic strategy with which the steric, electronic, and stereochemical properties of the ligands can be varied systematically. With the ligands in hand, we studied their reactivity towards different transition metal precursors, such as molybdenum, ruthenium, iron, nickel, palladium, and platinum. This has resulted in the preparation of a range of new pincer complexes, including various iron complexes, as well as the first heptacoordinated molybdenum pincer complexes and several pentacoordinated nickel complexes by using a controlled ligand decomposition pathway. In addition, we have investigated the use of some of the complexes as catalysts in different C-C coupling reactions: for example, the palladium PNP and PCP pincer complexes can be employed as catalysts in the well known Suzuki-Miyaura coupling, while the iron PNP complexes catalyze the coupling of aromatic aldehydes with ethyl diazoacetate under very mild reaction conditions to give selectively 3-hydroxyacrylates, which are otherwise difficult to prepare. While this Account presents an overview of current research on the chemistry of P-N bond containing pincer ligands and complexes, we believe that further investigations will give deeper insights into the reactivity and applicability of aminophosphine-based pincer complexes.     

A New Chiral P,N‐Ligand Derived from 1‐Phenylphospholane‐2‐carboxylic Acid (Phenyl‐P‐proline) for Palladium‐Catalyzed Asymmetric Allylic Substitution Reactions

New types of P,N‐ligands, cis‐ and trans‐ 3 , containing a tetrahydroisoquinoline skeleton as an N‐donor were synthesized from (1R,2S)‐1‐phenylphospholane‐2‐carboxylic acid (phenyl‐P‐proline, 1 ). The cis isomer, cis‐ 3 , was found to act as an excellent ligand in palladium‐catalyzed asymmetric allylic substitution reactions. The reactions of 1,3‐diphenyl‐2‐propenyl acetate ( 5 ) with several nucleophiles in the presence of [Pd(π‐allyl)Cl]₂, cis‐ 3 (Pd : ligand=1 : 2), and a base afforded the desired products in high yields with high enantioselectivity. It was suggested that these ligands did not serve as P,N‐bidentate ligands but as P‐monodentate ligands in these reactions.     

Presence of Dendritic Cell Subsets in Sentinel Nodes of Breast Cancer Patients Is Related to Nodal Burden

BACKGROUND: Sentinel lymph nodes (SLNs) are both the first site where breast cancer (BC) metastases form and where anti-tumoral immunity develops. Despite being the most potent antigen-presenting cells, dendritic cells (DCs) located in a nodal tissue can both promote or suppress immune response against cancer in SLNs. METHODS: In SLNs excisions obtained from 123 invasive BC patients, we performed immunohistochemistry (IHC) for CD1a, CD1c, DC-LAMP, and DC-SIGN to identify different DCs populations. Then we investigated the numbers of DCs subsets in tumor-free, micrometastatic, and macrometastatic SLNs with the use of a light microscope. RESULTS: We observed that CD1c+ and DC-SIGN+ DCs were more numerous in SLNs with a larger tumor size. More abundant intratumoral DC-LAMP+ population was related to a higher number of metastatic lymph nodes. Conversely, more abundant CD1a+ DCs were associated with a decreasing nodal burden in SLNs and a lower number of involved lymph nodes. Moreover, densities of the investigated DC populations differed with respect to tumor grade, HER2 overexpression, hormone receptor status, and histologic type of BC. CONCLUSIONS: According to their subtype, DCs are associated with either lower or higher nodal burden in SLNs from invasive BC patients. These relationships appear to be dependent not only on the maturation state of DCs but also on the histological and biological characteristics of the tumor.     

Development of Benzophenone‐Alkyne Bifunctional Sigma Receptor Ligands

Sigma (σ) receptors are unique non‐opioid binding sites that are associated with a broad range of disease states. Sigma‐2 receptors provide a promising target for diagnostic imaging and pharmacological interventions to curb tumor progression. Most recently, the progesterone receptor (PGRMC1, 25 kDa) has been shown to have σ2 receptor‐like binding properties, thus highlighting the need to understand the biological function of an 18 kDa protein that exhibits σ2‐like photoaffinity labeling (denoted here as σ2‐18k) but the amino acid sequence of which is not known. In order to provide new tools for the study of the σ2‐18k protein, we have developed bifunctional σ receptor ligands each bearing a benzophenone photo‐crosslinking moiety and an alkyne group to which an azide‐containing biotin affinity tag can be covalently attached through click chemistry after photo‐crosslinking. Although several compounds showed favorable σ2 binding properties, the highest affinity (2 nM ) and the greatest potency in blocking photolabeling of σ2‐18k by a radioactive photoaffinity ligand was shown by compound 22 . These benzophenone‐alkyne σ receptor ligands might therefore be amenable for studying the σ2‐18k protein through chemical biology approaches. To the best of our knowledge, these compounds represent the first reported benzophenone‐containing clickable σ receptor ligands, which might potentially have broad applications based on the “plugging in” of various tags.     

Understanding the Selectivity Mechanism of the Human Asialoglycoprotein Receptor (ASGP-R) toward Gal- and Man-type Ligands for Predicting Interactions with Exogenous Sugars

A practical approach for addressing the computer simulation of protein-carbohydrate interactions is described here. An articulated computational protocol was set up and validated by checking its ability to predict experimental data, available in the literature, and concerning the selectivity shown by the Carbohydrate Recognition Domain (CRD) of the human asialoglycoprotein receptor (ASGP-R) toward Gal-type ligands. Some required features responsible for the interactions were identified. Subsequently the same protocol was applied to monomer sugar molecules that constitute the building blocks for alginates and ulvans. Such sugar polymers may supply a low-cost source of rare sugars with a potential impact on several industrial applications, from pharmaceutical to fine chemical industry. An example of their applicative exploitation could be given by their use in developing biomaterial with adhesion properties toward hepatocytes, through interaction with the ASGP-R. Such a receptor has been already proposed as a target for exogenous molecules, specifically in the case of hepatocytes, for diagnostic and therapeutic purposes. The DOCK5.2 program was used to search optimal locations of the above ligands of interest into CRD binding site and to roughly estimate interaction energies. Finally, the binding ΔG of theoretical protein-ligand complexes was estimated by using the DelPhi program in which the solvation free energy is accounted for with a continuum solvent model, by solving the Poisson-Boltzmann equation. The structure analysis of the obtained complexes and their ΔG values suggest that one of the sugar monomers of interest shows the desired characteristics.     

Neuritogenic and Neuroprotective Properties of Peptide Agonists of the Fibroblast Growth Factor Receptor

Fibroblast growth factor receptors (FGFRs) interact with their cognate ligands, FGFs, and with a number of cell adhesion molecules (CAMs), such as the neural cell adhesion molecule (NCAM), mediating a wide range of events during the development and maintenance of the nervous system. Determination of protein structure, in silico modeling and biological studies have recently resulted in the identification of FGFR binding peptides derived from various FGFs and NCAM mimicking the effects of these molecules with regard to their neuritogenic and neuroprotective properties. This review focuses on recently developed functional peptide agonists of FGFR with possible therapeutic potential.