Synthesis of Sulfated Colominic Acids and Their Interaction with Fibroblast Growth Factors

Kunou, Megumi; Koizumi, Masako; Shimizu, Kiyotaka; Kawase, Makoto; Hatanaka, Kenichi

doi:10.1021/bm000011k

Cited by 26 publications

(25 citation statements)

References 41 publications

(83 reference statements)

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“…( Scheme 5 ). 49 As this method is not selective as to the location or number of sulfates incorporated on the sugar hydroxyl groups, and the molecules had been completely characterized after their initial synthesis, further NMR and mass spectral analysis was not conducted. Instead, elemental analysis for % sulfur (%S) was completed.…”

Section: Resultsmentioning

confidence: 99%

Evaluation of the Synthesis of Sialic Acid-PAMAM Glycodendrimers without the Use of Sugar Protecting Groups, and the Anti-HIV-1 Properties of These Compounds

et al. 2011

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A study was undertaken to evaluate the feasibility of synthesizing six sialic acid-PAMAM glycodendrimers using unprotected sialic acid in as few as 1-4 steps using two different reaction pathways, and to assess the sulfated derivatives for anti-HIV activity. The syntheses were accomplished through either the direct attachment of the sialic acid carboxyl group to amine-terminated PAMAM (a divergent-like approach) using BOP coupling, or by first reacting sialic acid with a polar bifunctional spacer molecule, attaching the sugar-linker to carboxy-terminated PAMAM (a convergent-like approach), and again using BOP-mediated coupling reactions. It was hypothesized that the latter approach would be the most successful method, as any steric congestion between the sialic acid and the PAMAM would be minimized using an intervening polar linker. However, the divergent-like synthesis proved to be the superior method, resulting in 11.4, 14, and 28% of the fully substituted generations 0, 1 and 2 sialic acid-PAMAM conjugates, respectively, as compared to 6.4% of only the generation -0.5 sialic acid-linker-PAMAM conjugate for the convergent-like method. Upon sulfation of the four glycodendrimers, binding capabilities to the recombinant HIV protein, gp120, were assessed using an ELISA assay. Compounds that showed promising binding characteristics were then further assessed for inhibition of HIV-1 infection using a well-characterized luciferase reporter gene neutralization assay. The generation 2 sulfated sialic acid-PAMAM glycodendrimer, sulfo-6, bearing 16 sialic acids with 11 sulfate groups incorporated at 4.03% sulfur content by weight, was found to inhibit all four HIV-1 strains tested in the low μM range.

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Section: Resultsmentioning

confidence: 99%

Evaluation of the Synthesis of Sialic Acid-PAMAM Glycodendrimers without the Use of Sugar Protecting Groups, and the Anti-HIV-1 Properties of These Compounds

et al. 2011

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“…Similarly, it has been reported that NCAM can associate with a receptor for members of signaling glial cell line-derived neutrophic factor (40). Synthetic sulfated polysialic acid binds to abasic FGF and basic FGF as strongly as heparin (41). It is thus possible that polysialic acid of NCAM on myotubes concentrates FGF and presents it to FGF receptors, thus providing a signal to stop further myoblast fusion.…”

Section: Discussionmentioning

confidence: 87%

Polysialic Acid and Mucin Type O-Glycans on the Neural Cell Adhesion Molecule Differentially Regulate Myoblast Fusion

Suzuki

Angata

Nakayama

et al. 2003

Journal of Biological Chemistry

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Polysialic acid attached to the neural cell adhesion molecule (NCAM) is thought to play a critical role in development. NCAM in muscle tissue contains a muscle-specific domain (MSD) to which mucin type O-glycans are attached. In the present study, using the C2C12 myoblast system, we show that NCAM containing MSD is increasingly expressed on the cell surface as myotubes form. Polysialic acid is primarily attached to N-glycans of NCAM, and polysialylated NCAM is expressed on the outer surface of myotube bundles. By transfecting cDNAs encoding wild type and mutant forms of NCAM, we found that NCAM containing MSD facilitates myoblast fusion, and this effect is diminished by mutating O-glycosylation sites at MSD. By contrast, forced expression of polysialic acid in early differentiation stages reduces myotube formation and delays the expression of NCAM containing the MSD domain. Strikingly, inhibition of polysialic acid synthesis by antisense DNA approach induced differentiation in both human rhabdomyosarcoma cells, which overexpress polysialic acid, and C2C12 cells. These results indicate that polysialic acid and mucin type O-glycans on NCAM differentially regulate myoblast fusion, playing critical roles in muscle development.During mammalian embryonic development, muscle development is initiated once mesenchymal cells commit to become myoblasts. Myoblasts then align and fuse, forming multinucleated myotubes, and mature myotubes are bundled together, forming sarcolemma. In parallel, each myotube starts contraction, receives innervation from motor and sensory neurons, and eventually forms muscle tissue. In this process, one of the most intriguing steps is myoblast fusion. Myoblast fusion consists of multiple steps: expression of the fusion competent phenotype, specific myoblast-myoblast recognition and alignment, cell adhesion and electrical coupling, and fusion of lipid bilayer membrane (1). It has been reported that anti-NCAM 1 antibody inhibits aggregation of fusion-competent chick embryo myoblasts (2), indicating that cell-cell adhesion via NCAM apparently initiates myoblast fusion. In addition, integrins, N-cadherin, VCAM, and VLA4 are thought to be involved (see Ref. 3 and references herein).NCAM is found in several isoforms due to alternative mRNA splicing of more than 19 exons. In mammalian brain, the glycosylphosphatidylinositol (GPI)-anchored 120-kDa isoform and transmembrane 140-and 180-kDa isoforms are primarily expressed. In muscles, three isoforms have been reported: a GPIanchored 125-kDa isoform and transmembrane 140-and 155-kDa isoforms (4). Muscle-specific domain (MSD) was identified in the cDNA of the 125-kDa NCAM isoform obtained from human skeletal muscle (5). MSD is encoded by four different exons, MSD1a, MSD1b, MSD1c, and codon AAG. The fulllength MSD sequence consists of 35 amino acids inserted between two fibronectin type III domains of NCAM. MSD insertion is observed only in skeletal muscle and heart and not in other tissues. O-Glycosylation of MSD was shown by peanut agglutinin (PNA) lecti...

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“…The proliferation of aortic endothelial cells strongly depends on the activity of endogenous fibroblast growth factor-2 (FGF-2) (Schweigerer et al, 1987;Sato and Rifkin, 1988). Although SCA binds FGF-2 and potentiates the mitogenic activity of fibroblastic 3T3-L1 cells, CA does not potentiate the FGF-2 activity (Kunou et al, 2000). It is possible that CA serves as a scavenger of endogenous FGF-2; as a result, the stimulation of endothelial cell proliferation by the growth factor is reduced.…”

Section: Discussionmentioning

confidence: 99%

Colominic acid inhibits the proliferation of cultured bovine aortic endothelial cells and injures their monolayers: Cell density-dependent effects prevented by sulfation

Yamamoto

Morita

Yamaguchi³

et al. 2006

Life Sciences

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Synthesis of Sulfated Colominic Acids and Their Interaction with Fibroblast Growth Factors

Cited by 26 publications

References 41 publications

Evaluation of the Synthesis of Sialic Acid-PAMAM Glycodendrimers without the Use of Sugar Protecting Groups, and the Anti-HIV-1 Properties of These Compounds

Evaluation of the Synthesis of Sialic Acid-PAMAM Glycodendrimers without the Use of Sugar Protecting Groups, and the Anti-HIV-1 Properties of These Compounds

Polysialic Acid and Mucin Type O-Glycans on the Neural Cell Adhesion Molecule Differentially Regulate Myoblast Fusion

Colominic acid inhibits the proliferation of cultured bovine aortic endothelial cells and injures their monolayers: Cell density-dependent effects prevented by sulfation

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