Controlled rapid synthesis and in vivo immunomodulatory effects of LM α(1,6)mannan with an amine linker

Bunthitsakda, Warunda; Leelayuwapan, Haris; Paha, Jiraporn; Kangwanrangsan, Niwat; Chawengkirttikul, Runglawan; Ponpuak, Marisa; Ruchirawat, Somsak; Boonyarattanakalin, Siwarutt

doi:10.1016/j.carbpol.2018.04.045

Cited by 10 publications

(3 citation statements)

References 35 publications

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“…However, this can be effectively avoided by setting control for comparative analysis. − Indeed, the current linker in our study is chemically stable and has difficulty in releasing the binding phytochemicals. Thus, we plan to introduce a distinct disulfide bond into the linker, which can be hydrolyzed to release the cross-linked phytochemicals upon dithiothreitol (DTT) treatment. , Taken together, we developed a convenient strategy for directly identifying the target proteins of phytochemicals. This strategy may open a new avenue for cellular target identification, bioactive compound discovery, and pharmacological mechanism study, especially for supercomplex molecular systems.…”

Section: Resultsmentioning

confidence: 99%

Gold Nanoparticle-Based Photo-Cross-Linking Strategy for Cellular Target Identification of Supercomplex Molecular Systems

Liao

Wang

et al. 2022

Anal. Chem.

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Cellular target identification plays an essential role in innovative drug development and pharmacological mechanism elucidation. However, very few practical experimental methodologies have been developed for identifying target proteins for supercomplex molecular systems such as biologically active phytochemicals or pharmaceutical compositions. To overcome this limitation, we synthesized gold nanoparticles (AuNPs) as solid scaffolds, which were bound with 4,4′-dihydroxybenzophenone (DHBP) as a photo-cross-linking group on the surface. Then, DHBP-modified AuNPs cross-linked various organic compounds from phytochemicals under ultraviolet radiation via carbene reactions, H–C bond insertion, for catalytic C–C bond formation. We next used the phytochemical-cross-linked AuNPs (phytoAuNPs) to pull down potential binding proteins from brain tissue lysate and identified 13 neuroprotective targets by mass spectrometry analysis. As an exemplary study, we selected Hsp60 as a crucial cellular target to further screen 14 target-binding compounds from phytochemicals through surface plasmon resonance (SPR) analysis, followed by Hsp60 activity detection and neuroprotective effect assay in cells. Collectively, this gold nanoparticle-based photo-cross-linking strategy can serve as a useful platform for discovering novel cellular targets for supercomplex molecular systems and help to explore pharmacological mechanisms and active substances.

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Section: Resultsmentioning

confidence: 99%

Gold Nanoparticle-Based Photo-Cross-Linking Strategy for Cellular Target Identification of Supercomplex Molecular Systems

Liao

Wang

et al. 2022

Anal. Chem.

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“…However, as glycosylation can also affect lipids, glycolipids can also be exploited as immunomodulatory adjuvants. A synthetically modified version of the glycolipid lipomannan, derived from M. tuberculosis, was used as a conjugate to tetanus toxoid in mice, which resulted in a synergistic boosting of IFNγ, IL-2, IP-10, and TNF-α levels in splenocytes of immunized mice (110).…”

Section: Adjuvants Are Key Determinants In Immune Modulationmentioning

confidence: 99%

Various Tastes of Sugar: The Potential of Glycosylation in Targeting and Modulating Human Immunity via C-Type Lectin Receptors

et al. 2020

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C-type lectin receptors (CLRs) are important in several immune regulatory processes. These receptors recognize glycans expressed by host cells or by pathogens. Whereas pathogens are recognized through their glycans, which leads to protective immunity, aberrant cellular glycans are now increasingly recognized as disease-driving factors in cancer, auto-immunity, and allergy. The vast variety of glycan structures translates into a wide spectrum of effects on the immune system ranging from immune suppression to hyper-inflammatory responses. CLRs have distinct expression patterns on antigen presenting cells (APCs) controlling their role in immunity. CLRs can also be exploited to selectively target specific APCs, modulate immune responses and enhance antigen presentation. Here we will discuss the role of glycans and their receptors in immunity as well as potential strategies for immune modulation. A special focus will be given to different dendritic cell subsets as these APCs are crucial orchestrators of immune responses in infections, cancer, auto-immunity and allergies. Furthermore, we will highlight the potential use of nanoscale lipid bi-layer structures (liposomes) in targeted immunotherapy.

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“…The identification of sugars that are mildly proinflammatory but not antigenic is key. The cell-wall capsules of pathogens such as Candida albicans, Mycobacterium tuberculosis, and Leishmania mexicana contain polymannoses with α-(1–2), α-(1–3), α-(1–6), β-(1–2), and β-(1–4) linkages. − While multivalent formulations of some branched oligomannoses have been investigated as anti-infective agents against viruses, parasites, and fungi, α-(1–6) branched oligomannosides are rarely studied and show mild proinflammatory properties. − In an effort to exploit the properties of such sugars toward the development of novel innate immunomodulators, we report here the synthesis and biological activity of short α-(1–6) oligomannoses in the context of monovalent and multivalent systems. As multivalent carriers of the sugars, we used water-soluble glycosylated-gold nanoparticles (2 nm) that are reduced and stabilized by thioglucoses. , These glyconanoparticles were then evaluated for their ability to trigger NF-κB signaling, secrete proinflammatory cytokines from RAW macrophages, and activate the complement system.…”

Section: Introductionmentioning

confidence: 99%

Synthetic Glyconanoparticles Modulate Innate Immunity but Not the Complement System

Ghosh

Priegue

Leelayuwapan

et al. 2022

ACS Appl. Bio Mater.

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Nanoparticles that modulate innate immunity can act as vaccine adjuvants and antigen carriers and are promising alternatives to conventional anticancer therapy. Nanoparticles might, upon contact with serum, activate the complement system that might in turn result in clearance and allergic reactions. Herein, we report that ultrasmall glyconanoparticles decorated with nonimmunogenic α-(1–6)-oligomannans trigger an innate immune response without drastically affecting the complement system. These negatively charged glyconanoparticles (10–15 nm) are stable in water and secrete proinflammatory cytokines from macrophages via the NF-κB signaling pathway. The glyconanoparticles can be used as immunomodulators for monotherapy or in combination with drugs and vaccines.

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Controlled rapid synthesis and in vivo immunomodulatory effects of LM α(1,6)mannan with an amine linker

Cited by 10 publications

References 35 publications

Gold Nanoparticle-Based Photo-Cross-Linking Strategy for Cellular Target Identification of Supercomplex Molecular Systems

Gold Nanoparticle-Based Photo-Cross-Linking Strategy for Cellular Target Identification of Supercomplex Molecular Systems

Various Tastes of Sugar: The Potential of Glycosylation in Targeting and Modulating Human Immunity via C-Type Lectin Receptors

Synthetic Glyconanoparticles Modulate Innate Immunity but Not the Complement System

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