Design and synthesis of multivalent α-1,2-trimannose-linked bioerodible microparticles for applications in immune response studies of Leishmania major infection

• Chelsea L. Rintelmann,
• Tara Grinnage-Pulley,
• Kathleen Ross,
• Daniel E. K. Kabotso,
• Angela Toepp,
• Anne Cowell,
• Christine Petersen,
• Balaji Narasimhan and
• Nicola Pohl

Beilstein J. Org. Chem. 2019, 15, 623–632, doi:10.3762/bjoc.15.58

• study the mechanisms of immune modulation. In this study, a new bioerodible polyanhydride microparticle was designed and conjugated with a glycodendrimer molecular probe. This molecular probe incorporates a pathogen-like multivalent display of α-1,2-trimannose, for which a more efficient synthesis was

• designed, with a tethered fluorophore. Further attachment of the glycodendrimer to a biocompatible, surface eroding microparticle allows for targeted uptake and internalization of the pathogen-associated oligosaccharide by phagocytic immune cells. The α-1,2-trimannose-linked bioerodible microparticles were

• . From the general design elements in Figure 3, we proposed the following synthetic motifs. For PRR binding, a dendrimeric scaffold provides a multivalent display of the α-1,2-trimannose glycoconjugate, similar to Leishmania LPG and additionally may promote glycodendrimer antigen presentation when

Glycodendrimers: tools to explore multivalent galectin-1 interactions

• Jonathan M. Cousin and
• Mary J. Cloninger

Beilstein J. Org. Chem. 2015, 11, 739–747, doi:10.3762/bjoc.11.84

• glycodendrimers provided competitive binding sites for galectin-1, which diverted galectin-1 from its typical function in cellular aggregation of DU145 cells. Keywords: dendrimer; galectin-1; glycodendrimer; multivalent; nanoparticle; Introduction Galectin-1 is a multivalent protein that mediates biological

• glycodendrimers would organize extracellular galectin-1 into aggregates that would influence the biological activity of galectin-1. To test this hypothesis, lactose functionalized dendrimers were used to nucleate the aggregation of galectin-1 into nanoparticles, and the sizes of the galectin-1/glycodendrimer

• nanoparticles were characterized using dynamic light scattering (DLS) and fluorescence microscopy (FM) when varying ratios of galectin-1 were added to the glycodendrimers. The galectin-1/glycodendrimer nanoparticle aggregates were then used to inhibit the galectin-1 induced aggregation of DU145 human prostate

The search for new amphiphiles: synthesis of a modular, high-throughput library

• George C. Feast,
• Thomas Lepitre,
• Xavier Mulet,
• Charlotte E. Conn,
• Oliver E. Hutt,
• G. Paul Savage and
• Calum J. Drummond

Beilstein J. Org. Chem. 2014, 10, 1578–1588, doi:10.3762/bjoc.10.163

• extensively reviewed [44][45][46][47][48][49][50]. Azido-sugars are known to react well under CuAAC reaction conditions [51][52] and have recently been used in the synthesis of a glycodendrimer library [53], as well as in our previous work on single-chain sugar amphiphiles [30]. Hence, a diverse sugar screen

Multivalent scaffolds induce galectin-3 aggregation into nanoparticles

• Candace K. Goodman,
• Mark L. Wolfenden,
• Pratima Nangia-Makker,
• Anna K. Michel,
• Avraham Raz and
• Mary J. Cloninger

Beilstein J. Org. Chem. 2014, 10, 1570–1577, doi:10.3762/bjoc.10.162

• . Here, we show that lactose-functionalized dendrimers interact with galectin-3 in a multivalent fashion to form aggregates. The glycodendrimer–galectin aggregates were characterized by dynamic light scattering and fluorescence microscopy methodologies and were found to be discrete particles that

• a ratio of galectin-3 to glycodendrimer of 220:1, 9:1, or 3:1. These ratios were chosen so that results obtained from experiments using a large excess, a significant excess, and a slight excess of galectin-3 could be compared. Regardless of the amount of excess galectin-3 that was used, the size and

• polydispersity of the aggregates was shown to increase with increasing dendrimer generation (Figure 1 and Table 1). The largest aggregates were observed for the 9:1 ratio of galectin-3 to glycodendrimer, and smaller aggregates were formed when a large excess or a very small excess of galectin-3 was used. This

Synthesis and solvodynamic diameter measurements of closely related mannodendrimers for the study of multivalent carbohydrate–protein interactions

• Yoann M. Chabre,
• Alex Papadopoulos,
• Alexandre A. Arnold and
• René Roy

Beilstein J. Org. Chem. 2014, 10, 1524–1535, doi:10.3762/bjoc.10.157

• the same criticism by providing unusually high (or too close) sugar densities. Also important and in spite of the two decades of glycodendrimer chemistry [7], there is still no general rule to allow predicting which structural parameters would be optimal for the binding interactions. In order to gain

• quantitative yield (Scheme 2). Complete spectral characterization (1H, 13C NMR and HRMS) concluded for the aforementioned structure having twelve atoms in the linking arm (see Supporting Information File 1). Analogously, the extended 9-mer glycodendrimer 17, possessing fourteen atoms between the anomeric

• = pulse length for bipolar pulses. All diffusion spectra were processed in Mat NMR [47]. Glycodendrimer synthesis Procedure A: multiple CuAAc couplings on polypropargylated cores To a solution of polypropargylated core (1.00 equiv) and complementary azido synthon (1.25 equiv/propargyl) in a THF/H2O

Low-generation dendrimers with a calixarene core and based on a chiral C₂-symmetric pyrrolidine as iminosugar mimics

• Marco Marradi,
• Stefano Cicchi,
• Francesco Sansone,
• Alessandro Casnati and
• Andrea Goti

Beilstein J. Org. Chem. 2012, 8, 951–957, doi:10.3762/bjoc.8.107

• calixarene core has only occasionally been explored. To the best of our knowledge, only one example in which a glycodendrimer was built on a calixarene core has been published [27], while no examples of iminosugar-based calixarene dendrimers have been reported so far. We report herein the synthesis of low