Herein the biodistributions and in vivo kinetics of chemically prepared neoglycoproteins are reviewed. Chemical methods can be used to conjugate various mono- and oligosaccharides onto a protein ...surface. The kinetics and organ-specific accumulation profiles of these glycoconjugates, which are introduced through intravenous injections, have been analyzed using conventional dissection studies as well as noninvasive methods such as single photon emission computed tomography, positron emission tomography and fluorescence imaging. These studies suggest that glycan-dependent protein distribution kinetics may be useful for pharmacological and diagnostic applications.
The enantioselective total synthesis of an unusual pentacyclic proaporphine alkaloid, (−)-misramine, was achieved. The synthetic strategy relied on an enantioselective intramolecular ...Friedel–Crafts-type 1,4-addition using an asymmetric organocatalyst to construct a spiroindane skeleton containing an all-carbon quaternary stereocenter and a double reductive amination of the keto-aldehyde to form a piperidine ring toward the end of the synthesis. This work is the first example of asymmetric synthesis of a proaporphine alkaloid.
The synthesis of organic compounds containing all-carbon quaternary stereocenters through the addition of allylmetals to aldehydes is still a challenge. In this account we describe two methods to ...achieve this transformation stereoselectively: one involves the zinc-mediated Barbier-type allylation and the other allylboration of a sugar-derived aldehyde. These methods were applied to the total synthesis of (+)-vibsanin A, and the synthesis of the tricyclic core of (−)-callophycoic acid A.
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Cytosporolide (Cytos) A–C, isolated from the fungus Cytospora sp., have anti-microbial activity, but their molecular targets in mammalian cells are unknown. We have previously ...reported the total synthesis of Cytos A by biomimetic hetero-Diels-Alder reaction. In this study, to examine the novel bioactivity of Cytos, we synthesized Cytos C and measured cell growth-inhibiting activities of 7 compounds, including Cytos A and C, in several human cancer cell lines. Among these compounds, Cytos C and tetradeoxycytosporolide A (TD-Cytos A), a model compound for the synthesis of Cytos A, had anti-proliferative effects on cancer cells, and TD-Cytos A exhibited stronger activity than Cytos C. In vitro topoisomerase-mediated DNA relaxing experiments showed that TD-Cytos A inhibited the activities of topoisomerase I and II, whereas Cytos C targeted only topoisomerase I. These data suggest that the anti-proliferative activities of Cytos correlate with the inhibition of topoisomerases and implicated TD-Cytos A as a novel anti-cancer drug that suppresses the activities of topoisomerase I and II.
A structural revision of clavilactone D, a potent inhibitor of protein tyrosine kinases, was achieved by total syntheses of two newly proposed structures. The syntheses relied on ...ring‐opening/ring‐closing metathesis, which transformed a cyclobutenecarboxylate into a γ‐butenolide. The syntheses confirmed that the correct structure of clavilactone D has an amino group at C‐3 instead of a hydroxy group at C‐2 in the originally proposed structure.
Easy D: A structural revision of clavilactone D was achieved by total syntheses of two newly proposed structures. The syntheses relied on ring‐opening/ring‐closing metathesis, which transformed a cyclobutenecarboxylate into a γ‐butenolide. The correct structure of clavilactone D has an amino group at C‐3 instead of a hydroxy group at C‐2 in the originally proposed structure.
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Multivalent interactions play an essential role in molecular recognition in living systems. These effects were employed to target tumor cells using albumin clusters bearing ∼10 ...molecules of asparagine-linked glycans (N-glycans). Noninvasive near-infrared fluorescence imaging clearly revealed A431 tumors implanted in BALB/cA-nu/nu mice after 1h in an N-glycan structure-dependent manner, thereby demonstrating the efficient use of glycan multivalency effects for tumor targeting in vivo.
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Vibsanin A is an 11-membered vibsane diterpenoid and is reported to induce myeloid cell differentiation via activation of protein kinase C (PKC) without tumor-promoting activity. ...Therefore, vibsanin A is thought to be an attractive compound for acute myeloid leukemia (AML) therapy. In this study, we synthesized vibsanin A analogs and compared the activity of these compounds for PKC activation and myeloid cell differentiation. We found that the hydroxymethyl group in vibsanin A is an important substituent to induce differentiation of AML cells. Collectively, our results showed the biochemical features of vibsanin A and provided new insights into the development of new antileukemic drugs.
Fluorescent carbon dots (CDs) represent a promising eco-friendly next-generation phosphor. However, most CDs exhibit broad photoluminescence (PL) spectra full width at half-maximum (fwhm) over 60 nm; ...few works on CDs with sharp PL spectra (fwhm less than 40 nm) have been reported. In addition, their syntheses and color tuning require harsh conditions of high temperatures, long reaction times, and high pressures with catalysts. Here, we successfully prepared narrow-bandwidth emissive CDs (fwhm of 27–40 nm) from phloroglucinol in a glycol solvent of 1,2-pentanediol at temperatures as low as 180 °C for a reaction duration of as short as 6 h under ambient conditions without any catalysts via an open reaction system in which dehydration and condensation reactions among phloroglucinol molecules were enhanced. We shifted the emission peak from 463 to 511 nm by selecting seven kinds of solvents with different polarities, that is, emission colors could be tuned from blue to green by taking advantage of fluorescence solvatochromism. The CD-dispersed polymer films showed a similar solvatochromic behavior and sharp PL spectra, verifying the feasibility of applying the CDs to displays with a wide color gamut.
Biodistribution and
in vivo
kinetics analysis of chemically prepared neoglycoproteins are reviewed. Various mono- and oligosaccharides were conjugated onto the protein surface by use of chemical ...methods. Their kinetic and organ-specific accumulation have extensively been studied after intravenous injection and analyzed by conventional dissection studies, as well as noninvasive methods, such as SPECT, PET, or fluorescence imaging. These studies clearly show the glycan-structure dependency on protein kinetics, which will provide promising possibilities for pharmacological and diagnostic applications.
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