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.
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•A highly amine-reactive “RIKEN click” probe was developed.•The probe was synthesized from commercially available materials with good yields.•“RIKEN click” reaction becomes one of the ...best techniques for glycan conjugation.
One pot double click strategy containing strain-promoted click-reaction followed by 6π-azaelectrocyclization (RIKEN click reaction) has worked well in the synthesis of multivalent homogeneous and heterogeneous N-glycoalbumins. We have slightly changed the structure of linker unsaturated aldehyde used in this method. As a result it can be easily synthesized from commercially available material and furthermore, the enhancement of its reactivity towards both click-reactions was observed. The data described in this Communications facilitate the usage of the double click strategy as a general method for the synthesis of a variety of neo-N-glycoproteins.
The gram-positive opportunistic bacterium
is one of the most common causatives of a variety of diseases including skin and skin structure infection or nosocomial catheter-associated infections. The ...biofilm formation that is an important virulence factor of this microorganism renders the antibiotic therapy ineffective, because biofilm-embedded bacteria exhibit strongly increased tolerance to antimicrobials. Here, we describe a novel 3-chloro-5(
)-(1
,2
,5
)-2-isopropyl-5-methylcyclohexyloxy-4-4-methylphenylsulfonyl-2(5
)-furanone (
), possessing a sulfonyl group and
-menthol moiety. Minimal inhibitory and bactericidal concentration values (MIC and MBC) of
were 10 and 40 mg/L, respectively, suggesting
biocidal properties.
exhibits pronounced activity against biofilm-embedded
and increases the efficacy of aminoglycosides (amikacin, gentamicin, and kanamycin) and benzalkonium chloride with fractional inhibitory concentration index values of 0.33-0.44 and 0.29, respectively, suggesting an alternative external treatment option, e.g., for wound infections. Moreover, low concentrations (0.5-1.3 mg/L) of
reduced the MICs of these antimicrobials twofold. By using confocal laser scanning microscopy and CFU counting, we show explicitly that
also restores the antimicrobial activity of gentamicin and ampicillin against
biofilms by several orders of magnitude. Biofilm structures were not destroyed but sterilized, with embedded cells being almost completely killed at twofold MBC. While
is quite toxic (CC
/MBC ratio 0.2), our data suggest that the
chemotype might be a promising starting point for the development of complex topical agents for combined anti-staphylococcal biofilm-therapies restoring the efficacy of some antibiotics against difficult to treat
biofilm.
Structurally well‐defined heterogeneous N‐glycoclusters are prepared on albumin via a double click procedure. The number of glycan molecules present, in addition to the spatial arrangement of glycans ...in the heterogeneous glycoclusters, plays an important role in the in vivo kinetics and organ‐selective accumulation through glycan pattern recognition mechanisms.
In Vivo Gold Complex Catalysis within Live Mice Tsubokura, Kazuki; Vong, Kenward K. H.; Pradipta, Ambara R. ...
Angewandte Chemie,
March 20, 2017, Letnik:
129, 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.
Die erste Metall‐katalysierte Reaktion in lebenden Mäusen basiert auf der Verwendung von Glycanen. Glycoalbumin‐AuIII‐Komplexe akkumulieren in spezifischen Organen, wo sie die Amidbildung zwischen einer Propargylestersonde und einem Amin eines nahen Proteins katalysieren. Die Organselektivität wurde durch Ganzkörperfluoreszenzbildgebung und die Analyse sezierter Gewebe bestätigt.
Natural glycoconjugates that form glycocalyx play important roles in various biological processes based on cell surface recognition through pattern recognition mechanisms. This work represents a new ...synthesis‐based screening strategy to efficiently target the cancer cells by higher‐order glycan pattern recognition in both cells and intact animals (mice). The use of the very fast, selective, and effective RIKEN click reaction (6π‐azaelectrocyclization of unsaturated imines) allows to synthesize and screen various structurally well‐defined glycoalbumins containing two and eventually four different N‐glycan structures in a very short time. The importance of glycan pattern recognition is exemplified in both cell‐ and mouse‐based experiments. The use of pattern recognition mechanisms for cell targeting represents a novel and promising strategy for the development of diagnostic, prophylactic, and therapeutic agents for various diseases including cancers.
Very fast and selective RIKEN click reaction allows to synthesize and screen various structurally well‐defined glycoalbumins containing four different N‐glycan structures in a very short time. Pattern recognition mechanisms for cell targeting in mice represent a novel and promising strategy for diagnostic, prophylactic, and therapeutic agents for various diseases, including cancers.
In article number 2004831, Almira Kurbangalieva, Katsunori Tanaka, and co‐workers successfully apply the glycan pattern recognition mechanisms for developing a promising cancer targeting strategy in ...both cell‐ and mouse‐based experiments. The use of the very fast, selective and effective RIKEN click reaction allows to synthesize and screen various structurally well‐defined glycoalbumins containing four different N‐glycan structures in a very short time, as novel diagnostic, prophylactic, and therapeutic agents.
In order to optimize the study of the anti-inflammatory activity of novel drugs, in the current study, we used simple in vitro test system, which included osmotic and free radical hemolysis of human ...erythrocytes and human platelets aggregation, to screen for potential anti-inflammatory activity of three newly developed (
S
)-naproxen derivatives. We selected one of them (L3), which performed in in vitro tests nearly as well as naproxen, and studied their anti-inflammatory effects on in vivo model of inflammation, induced by carragenan. L3 was comparable to naproxen in its anti-inflammatory effects, suggesting that the studied simple inexpensive in vitro tests of erythrocyte osmotic and free radical hemolysis and human platelets aggregation could be used for pre-screening of potential anti-inflammatory agents.
In vivo gold complex catalysis in living mice is described by K. Tanaka and co‐workers in their Communication on page 3579 ff. When attached to a glycocluster, gold catalysts can be delivered to a ...target organ in a higher organism where they perform a chemical transformation. This approach could enable the use of organometallic catalysts in therapy or diagnostics as they could catalyze the uncaging of therapeutic enzymes or the generation of active drugs at a target organ.
Invivo gold complex catalysis in living mice is described by K. Tanaka and co-workers in their Communication on page3579ff. When attached to a glycocluster, gold catalysts can be delivered to a ...target organ in a higher organism where they perform a chemical transformation. This approach could enable the use of organometallic catalysts in therapy or diagnostics as they could catalyze the uncaging of therapeutic enzymes or the generation of active drugs at a target organ.
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