854262-01-4Relevant articles and documents
Versatile Micropatterns of N-Heterocyclic Carbenes on Gold Surfaces: Increased Thermal and Pattern Stability with Enhanced Conductivity
Nguyen, D. Thao,Freitag, Matthias,K?rsgen, Martin,Lamping, Sebastian,Rühling, Andreas,Sch?fer, Andreas H.,Siekman, Martin H.,Arlinghaus, Heinrich F.,van der Wiel, Wilfred G.,Glorius, Frank,Ravoo, Bart Jan
, p. 11465 - 11469 (2018)
Patterned monolayers of N-heterocyclic carbenes (NHCs) on gold surfaces were obtained by microcontact printing of NHC–CO2 adducts and NHC(H)[HCO3] salts. The NHC-modified areas showed an increased conductivity compared to unmodified gold surface areas. Furthermore, the remaining surface areas could be modified with a second, azide-functionalized carbene, facilitating further applications and post-printing modifications. Thorough elucidation by a variety of analytical methods offers comprehensive evidence for the viability of the methodology reported here. The protocol enables facile access to versatile, microstructured NHC-modified gold surfaces with highly stable patterns, enhanced conductivity, and the option for further modification.
Multivalent, Stabilized Mannose-6-Phosphates for the Targeted Delivery of Toll-Like Receptor Ligands and Peptide Antigens
Reintjens, Niels R. M.,Tondini, Elena,Vis, Christopher,McGlinn, Toroa,Meeuwenoord, Nico J.,Hogervorst, Tim P.,Overkleeft, Herman S.,Filippov, Dmitri V.,van der Marel, Gijsbert A.,Ossendorp, Ferry,Codée, Jeroen D. C.
, p. 434 - 440 (2021)
Mannose-6-phosphate (M6P) is recognized by the mannose-6-phosphate receptor and plays an important role in the transport of cargo to the endosomes, making it an attractive tool to improve endosomal trafficking of vaccines. We describe herein the assembly of peptide antigen conjugates carrying clusters of mannose-6-C-phosphonates (M6Po). The M6Po's are stable M6P mimics that are resistant to cleavage of the phosphate group by endogenous phosphatases. Two different strategies for the incorporation of the M6Po clusters in the conjugate have been developed: the first relies on a “post-assembly” click approach employing an M6Po bearing an alkyne functionality; the second hinges on an M6Po C-glycoside amino acid building block that can be used in solid-phase peptide synthesis. The generated conjugates were further equipped with a TLR7 ligand to stimulate dendritic cell (DC) maturation. While antigen presentation is hindered by the presence of the M6Po clusters, the incorporation of the M6Po clusters leads to increased activation of DCs, thus demonstrating their potential in improving vaccine adjuvanticity by intraendosomally active TLR ligands.
Fullerene sugar balls
, p. 3860 - 3862 (2010)
Fullerene hexakis-adducts bearing 12 peripheral carbohydrate moieties have been prepared by grafting sugar derivatives onto the fullerene core through the copper mediated Huisgen 1,3-dipolar cycloaddition of azides and alkynes.
Selectivity of 1-O-Propargyl-D-Mannose Preparations
?ezanka, Michal,Dolensky, Bohumil,Krabicová, Ilona
, (2022/03/01)
Thanks to their ability to bind to specific biological receptors, mannosylated structures are examined in biomedical applications. One of the most common ways of linking a functional moiety to a structure is to use an azide-alkyne click reaction. Therefore, it is necessary to prepare and isolate a propargylated mannose derivative of high purity to maintain its bioactivity. Three known preparations of propargyl-α-mannopyranoside were revisited, and products were analysed by NMR spectroscopy. The preparations were shown to yield by-products that have not been described in the literature yet. Our experiments showed that one-step procedures could not provide pure propargyl-α-mannopyranoside, while a three-step procedure yielded the desired compound of high purity.
Anomeric alkylations and acylations of unprotected mono- and disaccharides mediated by pyridoneimine in aqueous solutions
Dey, Kalyan,Jayaraman, Narayanaswamy
supporting information, p. 2224 - 2227 (2022/02/17)
A site-specific deprotonation followed by alkylations and acylations of sugar hemiacetals to the corresponding alkyl glycosides and acylated sugars in aqueous solutions is disclosed herein. Pyridoneimine as a new base is developed to mediate the deprotonation of readily available sugar hemiacetals and further reactions with alkylation and acylation agents.
ENGINEERED ANTIBODIES AS MOLECULAR DEGRADERS THROUGH CELLULAR RECEPTORS
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Page/Page column 2, (2021/04/17)
The present disclosure provides, in one aspect, bifunctional compounds that can be used to promote or enhance degradation of certain circulating proteins. In certain embodiments, the circulating protein mediates a disease and/or disorder in a subject, and treatment or management of the disease and/or disorder requires degradation, removal, or reduction in concentration of the circulating protein in the subject. Thus, in certain embodiments, administration of a compound of the disclosure to the subject removes or reduces the circulation concentration of the circulating protein, thus treating, ameliorating, or preventing the disease and/or disorder.
Sequential acid-catalyzed alkyl glycosylation and oligomerization of unprotected carbohydrates
Spitzer, Lea,Lecommandoux, Sébastien,Cramail, Henri,Jér?me, Fran?ois
, p. 1361 - 1369 (2021/02/26)
An efficient method has been developed to synthesize end-functionalized oligosaccharides from unprotected monosaccharides in a one-pot/two-step approach. In the first step, mannose (and glucose) was functionalized with an alkyne group at the anomeric position through the Fisher-glycosylation reaction with propargyl alcohol as a glycosyl acceptor. In the second step, the functionalized monosaccharides were oligomerized and the experimental conditions were optimized by varying the temperature, time and the molar ratio between alcohol and sugar to reach a up to 8. The obtained oligosaccharides showed complete propargylation at their reducing chain-end and were successfully coupled to oleic acidviathe Huisgen reaction, affording bio-based surfactants.
Mannosylated Poly(ethylene imine) Copolymers Enhance saRNA Uptake and Expression in Human Skin Explants
Abdouni, Yamin,Becer, C. Remzi,Blakney, Anna K.,Bouton, Clément R.,Liu, Renjie,McKay, Paul F.,Shattock, Robin J.,Yilmaz, Gokhan
, p. 2482 - 2492 (2020/07/17)
Messenger RNA (mRNA) is a promising platform for both vaccines and therapeutics, and self-amplifying RNA (saRNA) is particularly advantageous, as it enables higher protein expression and dose minimization. Here, we present a delivery platform for targeted delivery of saRNA using mannosylated poly(ethylene imine) (PEI) enabled by the host-guest interaction between cyclodextrin and adamantane. We show that the host-guest complexation does not interfere with the electrostatic interaction with saRNA and observed that increasing the degree of mannosylation inhibited transfection efficiency in vitro, but enhanced the number of cells expressing GFP by 8-fold in human skin explants. Besides, increasing the ratio of glycopolymer to saRNA also enhanced the percentage of transfected cells ex vivo. We identified that these mannosylated PEIs specifically increased protein expression in the epithelial cells resident in human skin in a mannose-dependent manner. This platform is promising for further study of glycosylation of PEI and targeted saRNA delivery.
Targeted Delivery of a Mannose-Conjugated BODIPY Photosensitizer by Nanomicelles for Photodynamic Breast Cancer Therapy
Zhang, Quan,Cai, Ying,Li, Qiu-Yan,Hao, Lin-Na,Ma, Zheng,Wang, Xiao-Jun,Yin, Jian
, p. 14307 - 14315 (2017/09/25)
The targeted delivery of a photosensitizer (PS) with appropriate carriers represents an attractive means of selectively delivering cargo to target tissues or subcellular compartments for photodynamic therapy (PDT). Herein, a three-arm distyryl BODIPY derivative conjugated with mannose units (denoted by BTM) that can co-assemble with Tween 80 to form nanomicelles (BTM-NMs) for targeted PDT is reported. MDA-MB-231 breast cancer cells recognized and specifically internalized BTM-NMs via mannose-receptor-mediated endocytosis with preferential accumulation in the lysosomes. These NMs could disassemble in cell lysosomes and subsequently induce highly efficient singlet oxygen (1O2) generation upon light irradiation. 1O2 disrupted the lysosomal membrane and promoted the escape of BTM from the lysosome into the cytoplasm, thereby resulting in the efficient and selective killing of cancer cells through PDT. This study may provide a new strategy for designing targeted PDT systems to fight cancer.
Silver Oxide Mediated Monotosylation of Poly(ethylene glycol) (PEG): Heterobifunctional PEG via Polymer Desymmetrization
Pohlit, Hannah,Worm, Matthias,Langhanki, Jens,Berger-Nicoletti, Elena,Opatz, Till,Frey, Holger
, p. 9196 - 9206 (2017/12/26)
Heterobifunctional poly(ethylene glycol)s (PEGs) are key structures for bioconjugation in the context of the PEGylation strategy to enhance blood circulation times of, for example, peptide drugs or stealth liposomes. The formation of heterobifunctional PEGs from symmetric PEG diols is challenging because of limited yields of the targeted monofunctional product and difficulties associated with separation steps. On the basis of a detailed comparison of reaction conditions, we have investigated a polymer desymmetrization strategy to maximize the yields of monofunctional PEG tosylate. The tosylation reaction in the presence of the heterogeneous catalyst silver oxide and potassium iodide in a specific stoichiometric ratio proved to be highly efficient, resulting in 71-76% yield of monofunctional PEG depending on molecular weight, exceeding the expected value of 50% in a statistical reaction without addition of a catalyst. For characterization as well as for the preparative separation of monotosylated PEG, we developed a HPLC method, using an evaporative light scattering detector, enabling both analytical and semipreparative separation of monotosylated PEGs on gram scale up to 20 000 g mol-1. To demonstrate the efficiency of the procedure, an α-azido-ω-methacryloyl-PEG was prepared as a building block suitable for azide-alkyne click-type reactions that can be incorporated into polymer networks via radical polymerization. We click-functionalized α-azido-ω-methacryloyl-PEG with a mannose-functionalized alkyne to enable functionalization of nanogels for enhanced cellular uptake via the mannose receptor. The synthesis strategy is suitable for a broad range of applications in the field of PEGylation and for hydrogel and nanogel functionalization.
