106256-89-7Relevant articles and documents
Carbohydrate-naphthalene diimide conjugates as potential antiparasitic drugs: Synthesis, evaluation and structure-activity studies
Zuffo,Stucchi,Campos-Salinas,Cabello-Donayre,Martínez-García,Belmonte-Reche,Pérez-Victoria,Mergny,Freccero,Morales,Doria
, p. 54 - 66 (2019)
The neglected tropical diseases Human African Trypanosomiasis and leishmaniasis are caused by infection with trypanosomatid parasites Trypanosoma brucei and Leishmania spp, respectively. The genomes of these organisms contain multiple putative G-quadruplex (G4) forming sequences which have recently been proposed to mediate processes relevant for parasite survival. Therefore, G4 could be considered as potential targets for a novel approach towards the development of antiparasitic drugs. Recently, we have demonstrated that G4 ligands such as carbohydrate naphthalene diimide conjugates (carb-NDIs) possess notable antiparasitic activity. Herein, we have synthesized a new family of carb-NDIs, characterized by significant structural variability, and evaluated their anti-parasitic activity, with special focus on T. brucei. The interaction with relevant G4 sequences was evaluated in vitro through independent biophysical methods (FRET melting assays under competing conditions with double stranded DNA, circular dichroism and fluorescence titrations). Finally, flow cytometry and confocal microscopy experiments demonstrated that the conjugates exhibit excellent uptake into T. brucei parasites, localizing in the nuclei and kinetoplasts. Promising antiparasitic activity and selectivity against control mammalian cells, together with their peculiar mechanism of action, render the carb-NDI conjugates as suitable candidates for the development of an innovative treatment of trypanosomiasis.
Methyl b-lactoside [methyl b-D-galactopyranosyl- (1!4)-b-D-glucopyranoside] monohydrate: A solvomorphism study
Lin, Jieye,Oliver, Allen G.,Serianni, Anthony S.
, p. 668 - 674 (2021/10/14)
Methyl β-lactoside [methyl β-d-galacto-pyranosyl-(1→4)-β-d-gluco-pyran-oside] monohydrate, C13H24O11·H2O, (I), was obtained via spontaneous transformation of methyl β-lactoside methanol solvate, (II), during air-drying. Cremer-Pople puckering parameters indicate that the β-d-Galp (β-d-galacto-pyranos-yl) and β-d-Glcp (β-d-gluco-pyranos-yl) rings in (I) adopt slightly distorted 4 C 1 chair conformations, with the former distorted towards a boat form (B C1,C4) and the latter towards a twist-boat form (O5 S C2). Puckering parameters for (I) and (II) indicate that the conformation of the βGalp ring is slightly more affected than the βGlcp ring by the solvomorphism. Conformations of the terminal O-gly-co-sidic linkages in (I) and (II) are virtually identical, whereas those of the inter-nal O-glycosidic linkage show torsion-angle changes of 6° in both C - O bonds. The exocyclic hy-droxy-methyl group in the βGalp residue adopts a gt conformation (C4′ anti to O6′) in both (I) and (II), whereas that in the βGlcp residue adopts a gg (gauche-gauche) conformation (H5 anti to O6) in (II) and a gt (gauche-trans) conformation (C4 anti to O6) in (I). The latter conformational change is critical to the solvomorphism in that it allows water to participate in three hydrogen bonds in (I) as opposed to only two hydrogen bonds in (II), potentially producing a more energetically stable structure for (I) than for (II). Visual inspection of the crystalline lattice of (II) reveals channels in which methanol solvent resides and through which solvent might exchange during solvomorphism. These channels are less apparent in the crystalline lattice of (I).
Synthesis of functionalized copillar[4+1]arenes and rotaxane as heteromultivalent scaffolds
Chen, Wenzhang,Mohy Ei Dine, Tharwat,Vincent, Stéphane P.
supporting information, p. 492 - 495 (2021/01/25)
In this study, novel copillar[4+1]arenes were used as central heteromultivalent scaffolds via orthogonal couplings with a series of biologically relevant molecules such as carbohydrates, α-amino acids, biotin and phenylboronic acid. Further modifications by introducing maleimides or cyclooctyne groups provided molecular probes adapted to copper-free click chemistry. An octa-azidated fluorescent rotaxane bearing two distinct ligands was also generated in a fully controlled manner.
Self-Promoted Glycosylation for the Synthesis of β-N-Glycosyl Sulfonyl Amides
Ma?a, Patrycja,Pedersen, Christian Marcus
supporting information, p. 5685 - 5689 (2021/08/30)
N-Glycosyl N-sulfonyl amides have been synthesized by a self-promoted glycosylation, i. e. without any catalysts, promotors or additives. When the reactions were carried out at lower temperatures a mixture of N- and O-glycosides were observed, where the latter rearranged to give the β-N-glycosides at elevated temperatures. By this method sulfonylated asparagine derivatives can be selectively β-glycosylated in high yields by trichloroacetimidate glycosyl donors of different reactivity including protected glucosamine derivatives. The chemoselectivity in the glycosylations as well as the rearrangements from O-glycosides to β-N-glycosides gives information of the glycosylation mechanism. This method gives access to glycosyl sulfonyl amides under mild conditions.
Sialyllactoside and/or analogues, synthesis method and application
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, (2021/03/13)
The invention relates to sialyllactoside and/or analogues thereof, wherein the general formula is defined in the specification. According to the invention, the flexibility of a chemical method and thehigh regioselectivity and high efficiency of an enzyme
Synthesis of DNP-modified GM3-based anticancer vaccine and evaluation of its immunological activities for cancer immunotherapy
Lin, Han,Hong, Haofei,Feng, Lipeng,Shi, Jie,Zhou, Zhifang,Wu, Zhimeng
, p. 4041 - 4044 (2021/06/15)
Tumor-associated carbohydrate antigens (TACAs) are attractive targets for vaccine development. In this context, we described a strategy combining artificial TACA and glycoengineering for cancer vaccine development. A 2,4-ditrophenyl (DNP)-modified GM3 int
Ganglioside GM3 and/or analogue thereof, synthesis method and application of ganglioside GM3 and/or analogue thereof
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Paragraph 0153-0155; 0160-0161, (2020/06/20)
The invention relates to a method for synthesizing ganglioside GM3 and/or an analogue thereof. The method includes the following steps: (1) selecting a lactose donor represented by a general formula Iand/or an analogue thereof and selecting a sphingosine
Sialyloligosaccharide-quantum dot conjugate as well as preparation method and application thereof
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Paragraph 0193; 0195; 0197, (2020/03/17)
The invention relates to a sialyloligosaccharide-quantum dot conjugate, a preparation method of the conjugate, and an application of the conjugate in virus detection. The sialyloligosaccharide-quantumdot conjugate provided by the invention is prepared by
The design and synthesis of an α-Gal trisaccharide epitope that provides a highly specific anti-Gal immune response
Anraku, Kensaku,Sato, Shun,Jacob, Nicholas T.,Eubanks, Lisa M.,Ellis, Beverly A.,Janda, Kim D.
, p. 2979 - 2992 (2017/04/10)
Carbohydrate antigens displaying Galα(1,3)Gal epitopes are recognized by naturally occurring antibodies in humans. These anti-Gal antibodies comprise up to 1% of serum IgG and have been viewed as detrimental as they are responsible for hyperacute organ rejections. In order to model this condition, α(1,3)galactosyltransferase-knockout mice are inoculated against the Galα(1,3)Gal epitope. In our study, two α-Gal trisaccharide epitopes composed of either Galα(1,3)Galβ(1,4)GlcNAc or Galα(1,3)Galβ(1,4)Glc linked to a squaric acid ester moiety were examined for their ability to elicit immune responses in KO mice. Both target epitopes were synthesized using a two-component enzymatic system using modified disaccharide substrates containing a linker moiety for coupling. While both glycoconjugate vaccines induced the required high anti-Gal IgG antibody titers, it was found that this response had exquisite specificity for the Galα(1,3)Galβ(1,4)GlcNAc hapten used, with little cross reactivity with the Galα(1,3)Galβ(1,4)Glc hapten. Our findings indicate that while homogenous glycoconjugate vaccines provide high IgG titers, the carrier and adjuvanting factors can deviate the specificity to an antigenic determinant outside the purview of interest.
Glycosylated Reversible Addition-Fragmentation Chain Transfer Polymers with Varying Polyethylene Glycol Linkers Produce Different Short Interfering RNA Uptake, Gene Silencing, and Toxicity Profiles
Williams, Elizabeth G. L.,Hutt, Oliver E.,Hinton, Tracey M.,Larnaudie, Sophie C.,Le, Tam,Macdonald, James M.,Gunatillake, Pathiraja,Thang, San H.,Duggan, Peter J.
, p. 4099 - 4112 (2017/12/26)
Achieving efficient and targeted delivery of short interfering (siRNA) is an important research challenge to overcome to render highly promising siRNA therapies clinically successful. Challenges exist in designing synthetic carriers for these RNAi constructs that provide protection against serum degradation, extended blood retention times, effective cellular uptake through a variety of uptake mechanisms, endosomal escape, and efficient cargo release. These challenges have resulted in a significant body of research and led to many important findings about the chemical composition and structural layout of the delivery vector for optimal gene silencing. The challenge of targeted delivery vectors remains, and strategies to take advantage of nature's self-selective cellular uptake mechanisms for specific organ cells, such as the liver, have enabled researchers to step closer to achieving this goal. In this work, we report the design, synthesis, and biological evaluation of a novel polymeric delivery vector incorporating galactose moieties to target hepatic cells through clathrin-mediated endocytosis at asialoglycoprotein receptors. An investigation into the density of carbohydrate functionality and its distance from the polymer backbone is conducted using reversible addition-fragmentation chain transfer polymerization and postpolymerization modification.
