A 75 years-old man presented with the edema and cyanosis of the right lower extremity. A lower limb ultrasound and Enhanced CT revealed the 31 mm right popliteal artery aneurysm with thrombus which ...caused blue tow syndrome. Endovascular repair with insertion of a stent graft Gore VIABAHN was performed. Angiography was performed with and without the knee bent, and an appropriate landing zone was confirmed to select the device size. No complication was observed even after operation, and the 9-month follow-up Enhanced CT showed the aneurysm well-thrombosed and no endoleak.
Enzyme biosensors are useful tools that can monitor rapid changes in metabolite levels in real-time. However, current approaches are largely constrained to metabolites within a limited chemical ...space. With the rising development of artificial metalloenzymes (ArM), a unique opportunity exists to design biosensors from the ground-up for metabolites that are difficult to detect using current technologies. Here we present the design and development of the ArM ethylene probe (AEP), where an albumin scaffold is used to solubilize and protect a quenched ruthenium catalyst. In the presence of the phytohormone ethylene, cross metathesis can occur to produce fluorescence. The probe can be used to detect both exogenous- and endogenous-induced changes to ethylene biosynthesis in fruits and leaves. Overall, this work represents an example of an ArM biosensor, designed specifically for the spatial and temporal detection of a biological metabolite previously not accessible using enzyme biosensors.
Metal-based uncaging of biomolecules has become an emerging approach for in vivo applications, which is largely due to the advantageous bioorthogonality of abiotic transition metals. Adding to the ...library of metal-cleavable protecting groups, this work introduces the 2-alkynylbenzamide (Ayba) moiety for the gold-triggered release of secondary amines under mild and physiological conditions. Studies were further performed to highlight some intrinsic benefits of the Ayba protecting group, which are (1) its amenable nature to derivatization for manipulating prodrug properties, and (2) its orthogonality with other commonly used transition metals like palladium and ruthenium. With a focus on highlighting its application for anticancer drug therapies, this study successfully shows that gold-triggered conversion of Ayba-protected prodrugs into bioactive anticancer drugs ( i.e. doxorubicin, endoxifen) can proceed effectively in cell-based assays.
The CRISPR/Cas9 system enables the editing of genomes of numerous organisms through the induction of the double-strand breaks (DSB) at specific chromosomal targets. We improved the CRISPR/Cas9 system ...to ease the direct introduction of a point mutation or a tagging sequence into the chromosome by combining it with the noncanonical homology-directed DNA repair (HDR) based genome editing in fission yeast. We constructed convenient cloning vectors, which possessed a guide RNA (gRNA) expression module, or the humanized
gene that is expressed under the control of an inducible promoter to avoid the needless expression, or both a gRNA and Cas9 gene. Using this system, we attempted the short-homology-mediated genome editing and found that the HDR pathway provides high-frequency genome editing at target loci without the need of a long donor DNA. Using short oligonucleotides, we successfully introduced point mutations into two target genes at high frequency. We also precisely integrated the sequences for epitope and GFP tagging using donor DNA possessing short homology into the target loci, which enabled us to obtain cells expressing N-terminally tagged fusion proteins. This system could expedite genome editing in fission yeast, and could be applicable to other organisms.
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•Heterogeneous glycoalbumins containing two non-identical N-glycans were prepared.•Local glycan heterogeneity affected the cancer accumulation.•Glycan pattern recognition is promising ...method for cancer targeting.
The preparation of heterogeneous glycoclusters on human serum albumin, containing two structurally non-identical N-glycans, is reported. In agreement with the cell-based interaction data, the trivial structural difference in local glycan heterogeneity can affect the in vivo distribution and cancer accumulation.
Controlling the stereoselectivity of 1,2-
glycosylation is one of the most challenging tasks in the chemical synthesis of glycans. There are various 1,2-
glycosides in nature, such as α-glucoside and ...β-mannoside in glycoproteins, glycolipids, proteoglycans, microbial polysaccharides, and bioactive natural products. In the structure of polysaccharides such as α-glucan, 1,2-
α-glucosides were found to be the major linkage between the glucopyranosides. Various regioisomeric linkages, 1→3, 1→4, and 1→6 for the backbone structure, and 1→2/3/4/6 for branching in the polysaccharide as well as in the oligosaccharides were identified. To achieve highly stereoselective 1,2-
glycosylation, including α-glucosylation, a number of strategies using inter- and intra-molecular methodologies have been explored. Recently, Zn salt-mediated
glycosylation has been developed and applied to the synthesis of various 1,2-
linkages, such as α-glucoside and β-mannoside, via the 1,2-
glycosylation pathway and β-galactoside 1,4/6-
induction. Furthermore, the synthesis of various structures of α-glucans has been achieved using the recent progressive stereoselective 1,2-
glycosylation reactions. In this review, recent advances in stereoselective 1,2-
glycosylation, particularly focused on α-glucosylation, and their applications in the construction of linear and branched α-glucans are summarized.
In Vivo Gold Complex Catalysis within Live Mice Tsubokura, Kazuki; Vong, Kenward K. H.; Pradipta, Ambara R. ...
Angewandte Chemie International Edition,
March 20, 2017, Letnik:
56, Številka:
13
Journal Article
Recenzirano
Metal complex catalysis within biological systems is largely limited to cell and bacterial systems. In this work, a glycoalbumin–AuIII complex was designed and developed that enables organ‐specific, ...localized propargyl ester amidation with nearby proteins within live mice. The targeted reactivity can be imaged through the use of Cy7.5‐ and TAMRA‐linked propargyl ester based fluorescent probes. This targeting system could enable the exploitation of other metal catalysis strategies for biomedical and clinical applications.
The first metal‐catalyzed reaction that proceeds within live mice is based on a targeting approach with glycans. Glycoalbumin–AuIII complexes can be accumulated in specific organs where they catalyze amide bond formation between a propargyl ester probe and amine groups on nearby proteins. The selective targeting was confirmed by whole body fluorescence imaging and analysis of dissected tissues.
A chemical synthesis of a core fucose containing N-glycan was achieved. Asparagine was introduced at an early stage of the synthesis, and the sugar chain was convergently elongated. As for the ...fragment synthesis, we reinvestigated α-sialylation, β-mannosylation, and N-glycosylation to reveal that precise temperature control was essential for these glycosylations. Intermolecular hydrogen bonds involving acetamide groups were found to reduce the reactivity in glycosylations: the protection of NHAc as NAc2 dramatically improved the reactivity. The dodecasaccharide–asparagine framework was constructed via the (4 + 4) glycosylation and the (4 + 8) glycosylation using the tetrasaccharide donor and the tetrasaccharide–asparagine acceptor. An ether-type solvent enhanced the yields of these key glycosylations between large substrates. After the whole deprotection of the dodecasaccharide, the target N-glycan was obtained.
-Arabinofuranosidases (Ara
ases) degrade the arabinan in the cell wall of acid-fast bacteria like Mycobacterium. Synthetic arabinan fragment probes could be used to investigate the function of
-Ara
...ases, whose synthetic studies had been reported previously. The homologue of one of the arabinan-degrading enzymes, exo-α-
-Ara
ase, was identified as BBDE_2040 from
. BBDE_2040, which is a homologue of α-
-Ara
ase, was also observed to hydrolyze α-
-fructofuranosides (Fru
), whose linkage is found in food. In this paper, we present synthetic studies and structural analysis of the α-
-Ara
and α-
-Fru
derivatives as substrates and products of the enzymatic reaction for a thorough examination of BBDE_2040. The results indicated that BBDE_2040 is a glycoside hydrolase (GH) family 172 difructose dianhydride I synthase/hydrolase and an anomer-retaining GH.
Rare sugars are known for their ability to suppress postprandial blood glucose levels. Therefore, oligosaccharides and disaccharides derived from rare sugars could potentially serve as functional ...sweeteners. A disaccharide α-d-allopyranosyl-(1→2)-β-d-psicofuranoside mimicking sucrose was synthesized from rare monosaccharides D-allose and D-psicose. Glycosylation using the intermolecular aglycon delivery (IAD) method was employed to selectively form 1,2-
α-glycosidic linkages of the allopyranose residues. Moreover, β-selective psicofuranosylation was performed using a psicofuranosyl acceptor with 1,3,4,6-tetra-
-benzoyl groups. This is the first report on the synthesis of non-reducing disaccharides comprising only rare d-sugars by IAD using protected ketose as a unique acceptor; additionally, this approach is expected to be applicable to the synthesis of functional sweeteners.
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