Akira Kawamura's research while affiliated with CUNY Graduate Center and other places

Publications (25)

Article
Full-text available
2,5-diketopiperazines (DKPs) are cyclic dipeptides ubiquitously found in nature. In particular, cyclo(Phe-Pro), cyclo(Leu-Pro), and cyclo(Val-Pro) are frequently detected in many microbial cultures. Each of these DKPs has four possible stereoisomers due to the presence of two chirality centers. However, absolute configurations of natural DKPs are o...
Article
Microbes use signaling factors for intraspecies and interspecies communications. While many intraspecies signaling factors have been found and characterized, discovery of factors for interspecies communication is lagging behind. To facilitate the discovery of such factors, we explored the potential of a mixed microbial culture (MMC) derived from wh...
Article
There are many immune‐boosting medicinal plants that can potently activate innate immune cells. Recent studies indicate that the active factors of some immune‐boosting plants are lipopolysaccharides (LPSs) of plant‐associated bacteria. However, little is currently known about the potential risk and benefit of LPSs in medicinal plants. To facilitate...
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Full-text available
Background: Angelica sinensis is a medicinal plant known for a variety of biological effects, including its ability to stimulate innate immune cells in humans. Recent studies indicate that the immunostimulatory activity of A. sinensis arises from microbe-associated molecular patterns (MAMPs) of plant-associated bacteria. However, it is unknown whic...
Article
In this issue of Cell Chemical Biology, Pezacki and co-workers (Sherratt et al., 2017) report a simple method to metabolically label viable bacteria, which can be used to detect and capture foodborne pathogens. The method may also find many other applications because it can be used to recover live cells, pathogens and non-pathogens, from various bi...
Article
A CD1d-binding, invariant (i) natural killer T (NKT)-cell stimulatory glycolipid, α-Galactosylceramide (αGalCer), has been shown to act as an adjuvant. We previously identified a fluorinated phenyl ring-modified αGalCer analog, 7DW8-5, displaying a higher binding affinity for CD1d molecule and more potent adjuvant activity than αGalCer. In the pres...
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Ginkgolides are terpene trilactones in Ginkgo biloba, a popular medicinal herb for memory disorders. Although ginkgolides are known for various neurobiological effects, their macromolecular target in brain is unknown. In this work, we employed benzophenone derivatives of ginkgolides to identify their binding-target in brain. Photolabeling of bovine...
Article
Benzophenone is a popular photophore for photoaffinity-labeling. It is also an important framework for drug development; many drugs contain benzophenone or analogous frameworks. The current work reports that benzophenone and its analogs bind to human glyoxalase 1. The binding, however, has little effect on the catalytic activity of this enzyme. The...
Article
Full-text available
A CD1d-binding glycolipid, α-Galactosylceramide (αGalCer), activates invariant NK T cells and acts as an adjuvant. We previously identified a fluorinated phenyl ring-modified αGalCer analog, 7DW8-5, displaying nearly 100-fold stronger CD1d binding affinity. In the current study, 7DW8-5 was found to exert a more potent adjuvant effect than αGalCer f...
Article
Juzen-taiho-to (JTT) is an immune-boosting formulation of ten medicinal herbs. It is used clinically in East Asia to boost the human immune functions. The active factors in JTT have not been clarified. But, existing evidence suggests that lipopolysaccharide (LPS)-like factors contribute to the activity. To examine this possibility, JTT was subjecte...
Article
Juzen-taiho-to is an immunostimulatory herbal formulation that is clinically used in East Asia for cancer patients undergoing chemotherapy and radiation. The formulation stimulates various leukocytes, including T, B, and NK cells and macrophages. Although Juzen-taiho-to is known to contain numerous compounds with various pharmacological activities,...
Article
Reproducibility is an important issue in biological characterization of drug candidates and natural products. It is not uncommon to encounter cases in which supposedly the same sample exhibits very different biological activities. During our characterization of macrophage-stimulatory lipids from herbal medicine, it was found that the potency of the...
Article
The tetrahydrofuran (THF) containing annonaceous acetogenins (AAs) are attractive candidates for drug development because of their potent cytotoxicity against a wide range of tumors and their relatively simple and robust structures. Replacement of the THF segment with a sugar residue may deliver analogues with improved tumor selectivity and pharmac...
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Benzophenone photoprobes represent powerful tools for chemical proteomics. Upon UV irradiation, a benzophenone photoprobe can selectively form a covalent bond with its target protein in complex protein mixtures. Thus, photoprobes can be used to profile a wide variety of proteins in complex proteomes. This chapter describes simple protocols to deriv...
Article
Extracellular heat shock proteins (eHsps) in blood circulation have been associated with various diseases, including cancer. However, the lack of methods to enrich eHsps from serum samples has hampered the characterization of eHsps. This Letter presents our serendipitous finding that the monomeric avidin resin can serve as an affinity resin to enri...
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A new diterpene with a fused 5-8-5 ring system was isolated from the fermentation broth of a soil actinomycete. The stereochemistry at C-15 was determined in an unusual manner using a decomposition product.
Article
Biomarker-guided screening is a multidisciplinary approach that can be used to facilitate early drug discovery from natural products. By integrating powerful genomic tools and the rapidly expanding knowledge of biomarkers, the screening systematically identifies compounds with therapeutic potential from herbal medicines. Compounds identified throug...
Article
Full-text available
Antigen presenting molecules play an important role in both innate and adoptive immune responses by priming and activating T cells. Among them, CD1 molecules have been identified to present both exogenous and endogenous lipid antigens to CD1-restricted T cells. The involvement of CD1-restricted T cells in autoimmune diseases and in defense against...
Article
Benzophenone photophores are employed widely for photoaffinity-labeling studies. Photolabeling with benzophenone, however, is hardly a routine experiment. Even when a photoprobe binds to its target, photocrosslinking does not necessarily occur. This is because photolabeling by benzophenone is affected by many factors other than target-binding, such...
Article
A highly convergent synthesis of mono-tetrahydrofuran (THF) containing acetogenins, that is based on the cross-metathesis of THF and butenolide alkene precursors, was developed. This methodology was applied to the epimers of the C-9 alcohol of 4-deoxyannoreticuin, in an attempt to assign the configuration at this position in the naturally occurring...
Article
From Toki-shakuyaku-san, an herbal formulation for 'cleansing stagnated blood,' a key gene regulatory compound was purified and identified through a screening based on DNA microarray and real-time PCR.
Article
A molecular probe that selectively tags Lck, a Src-family kinase, was developed. This probe was one of many compounds originally designed to target the active site of tyrosine kinases in general. To our surprise, however, the probe almost exclusively labeled Lck even in a lysate of Jurkat cells. This finding led us to further characterize this prob...
Article
A screening methodology called 'genomic screening' was established to identify natural products that can regulate cellular gene expression. Application of genomic screening to Keishi-bukuryo-gan (KBG), a Japanese herbal medicine formulation, identified a previously unnoticed transcriptional effect by linoleic acid, a known KBG component. The approa...
Article
DNA microarrays were employed to compare gene expression in a thermotolerant, nalidixic acid-resistant mutant of Escherichia coli with that of the parental strain. When grown at 37 degrees C, up-regulated genes in the mutant included those coding for multiple antibiotic resistance proteins and enzymes for the degradation of small molecules, whereas...
Article
Chirality plays a central role in various biological recognition processes. Here a methodology was developed to utilize chiral recognition processes for the selective biotinylation of proteins in crude cell lysates. Two pairs of diastereomeric probes containing benzophenone and biotin were prepared through solid-phase synthesis. Protein-binding sel...

Citations

... During our recent study on mixed microbial cultures (MMCs), which were derived from microbiotas of plants and environmental samples [13], we analyzed our datasets of liquid chromatography tandem mass spectrometry (LC/MS/MS) with GNPS (Global Natural Products Social Molecular Networking), which is a web-based MS database, to characterize metabolites in complex mixtures [14]. The GNPS analysis revealed a series of DKPs, namely cyclo(Phe-Pro), cyclo(Leu-Pro), and cyclo(Val-Pro), in MMCs (Supplementary Figure S1). ...
... Our previous research on the physiological response of AM showed that circulatory TNFα and IFNγ levels were significantly increased in human serum following in vivo administration of AM [26]. PMBCs are a mixture of mostly lymphocytes (T-cells, B-cells, and natural killer cells) as well as monocytes, macrophages, and dendritic cells, that are used frequently in immunological research cell-culture studies [71][72][73]. Based on our previous research findings, we chose to look at the expression of TNFα and IFNγ in human PMBCs following treatment with AM, with and without LPS/lipoprotein removal. ...
... This supports previous research where Pugh et al. (2008) attributed the majority of immune enhancing botanicals' in vitro macrophage activating properties to the presence of both LPS and bacterial lipoproteins acting through TLR4 and TLR2, respectively [43]. In addition, extracts from specific botanicals, including Angelica sinensis, Ashwaganda, and Echinacea purpurea have been shown to have immune stimulatory activity linked to plant-associated bacteria [44,[84][85]. Furthermore, there may be other synergistic ...
... Many studies have revealed the beneficial adjuvanting effects of glycolipids in mice. 45,50,51 The a-GalCer analog 7DW8-5 has emerged as a promising candidate adjuvant for malaria vaccines, demonstrating efficacy in both mice and NHPs. [43][44][45] Mechanistically, 7DW8-5 is presented on CD1d molecules to iNKT cells (reviewed in reference 52), which are found normally patrolling liver sinusoids in mice. ...
... One of the macromolecular targets of GA is α-tubulin in microtubules (MT) (Kawamura et al., 2016). In fact, GA was found not to affect MT-assembly, but it selectively modulates the post-translational modifications (PTMs) of α-tubulin, particularly, the detyrosination-tyrosination cycle. ...
... The labeling at the lipid interface was identical in the resting and desensitized states, while labeling in the ion channel was reduced by 90% in the desensitized state, and the labeling of δPhe-232/δPro-286/ δIle-288 only occurred in the desensitized state. 68 Mihai et al. 152 summarized those biologically active agents that contain an intrinsic BP moiety, including fenofibrate (92) lipidlowering agent that targets PPARα ( Figure 61) and doxorubicin (anticancer agent that targets DNA). Note that in an earlier study 14 C-doxorubicin labeled a 170 kDa Ca 2+ -releasing protein. ...
... However, while vegetable leaves are well populated with bacteria including potential probiotic acting Lactobacillus strains [34][35][36][37], so far, plant-derived produce has only been considered as vehicles of probiotic cultures [38,39]. A detailed understanding of how probiotic bacteria colonize leafy vegetables or herbs would enable future approaches to enrich these tissues with the respective bacterial strains to elevate vegetable leaves beyond their basic nutritional values. ...
... Liu et al. reported that JTT promoted the differentiation of transplanted bone marrow cells into microglia in the injured mouse brain [9]. Takaoka et al. reported that glycolipids of JTT stimulated macrophages [27]. Furthermore, Onishi et al. reported that JTT activated macrophages and T cells and prevented the metastasis of colon cancer cells to the liver in mice [13]. ...
... 14 Nnps are usually composed of proteins, polysaccharides, and lipids. [15][16][17][18][19] Importantly, Nnps can adsorb active constituents, 17,[20][21][22] carry them for absorption, 20,23,24 and distribute them to target tissues. 17 These results suggest that Nnps may affect the pharmaceutical and pharmacokinetic properties of the active constituents in herbal extracts. ...