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.
Selective cell tagging (SeCT) therapy is a strategy for labeling a targeted cell with certain chemical moieties via a catalytic chemical transformation in order to elicit a therapeutic effect. ...Herein, we report a cancer therapy based on targeted cell surface tagging with proapoptotic peptides (Ac-GGKLFG-X; X = reactive group) that induce apoptosis when attached to the cell surface. Using either Au-catalyzed amidation or Ru-catalyzed alkylation, these proapoptotic peptides showed excellent therapeutic effects both in vitro and in vivo . In particular, co-treatment with proapoptotic peptide and the carrier–Ru complex significantly and synergistically inhibited tumor growth and prolonged survival rate of tumor-bearing mice after only a single injection. This is the first report of Ru catalyst application in vivo , and this approach could be used in SeCT for cancer therapy.
A bio‐inspired cascade reaction has been developed for the construction of the marine natural product ageladine A and a de novo array of its N1‐substituted derivatives. This cascade features a ...2‐aminoimidazole formation that is modeled after an arginine post‐translational modification and an aza‐electrocyclization. It can be effectively carried out in a one‐pot procedure from simple anilines or guanidines, leading to structural analogues of ageladine A that had been otherwise synthetically inaccessible. We found that some compounds out of this structurally novel library show a significant activity in modulating the neural differentiation. Namely, these compounds selectively activate or inhibit the differentiation of neural stem cells to neurons, while being negligible in the differentiation to astrocytes. This study represents a successful case in which the native biofunction of a natural product could be altered by structural modifications.
One‐pot wonder! A bio‐inspired one‐pot cascade reaction, which features a 2‐aminoimidazole formation with subsequent aza‐electrocyclization for the construction of the marine natural product ageladine A and its derivatives, has been developed. Some of these derivatives selectively activated or inhibited the differentiation of neural stem cells to neurons. Ageladine A was thus transformed into a new selective neural‐differentiation modulator.
This study presents the early framework of selective cell tagging (SeCT) therapy, which is the concept of preferentially labeling specific cells in vivo with chemical moieties that can elicit a ...therapeutic response. Using glycosylated artificial metalloenzyme (GArM)-based protein labeling, this study reports two separate functional strategies. In one approach, early tumor onset can be suppressed by tagging cancer cells in living mice with an integrin-blocking cyclic-Arg-Gly-Asp (cRGD) moiety, thereby disrupting cell adhesion onto the extracellular matrix. In another approach, tumor growth in mice can be reduced by tagging with a cytotoxic doxorubicin moiety. Subsequent cell death occurs following internalization and drug release. Overall, experiments have shown that mouse populations receiving the mixture of SeCT labeling reagents exhibited a significant delay/reduction in tumor onset and growth compared with controls. Highlighting its adaptability, this work represents a foundational step for further development of SeCT therapy and its potential therapeutic applications.
A convenient route to RIKEN click probes for glycoconjugation to the amino groups of lysines was established. N-Glycoclusters prepared with human serum albumin by the new method showed the same cell ...interaction profiles as those synthesized previously. The new route has thus significantly expanding the applicability to glycoconjugation and drug delivery systems.
Celotno besedilo
Dostopno za:
BFBNIB, DOBA, GIS, IJS, IZUM, KILJ, KISLJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
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.
A bio-inspired cascade reaction has been developed for the construction of the marine natural product ageladineA and a de novo array of its N1-substituted derivatives. This cascade features a ...2-aminoimidazole formation that is modeled after an arginine post-translational modification and an aza-electrocyclization. It can be effectively carried out in a one-pot procedure from simple anilines or guanidines, leading to structural analogues of ageladineA that had been otherwise synthetically inaccessible. We found that some compounds out of this structurally novel library show a significant activity in modulating the neural differentiation. Namely, these compounds selectively activate or inhibit the differentiation of neural stem cells to neurons, while being negligible in the differentiation to astrocytes. This study represents a successful case in which the native biofunction of a natural product could be altered by structural modifications. One-pot wonder! A bio-inspired one-pot cascade reaction, which features a 2-aminoimidazole formation with subsequent aza-electrocyclization for the construction of the marine natural product ageladineA and its derivatives, has been developed. Some of these derivatives selectively activated or inhibited the differentiation of neural stem cells to neurons. AgeladineA was thus transformed into a new selective neural-differentiation modulator.
Rapidly growing cancer cells have increased levels of intracellular polyamines compared to normal, healthy tissues. Based on the selective reactivity of glycine propargyl esters, probes were ...synthesized that show evidence for selective polyamine reactivity, which was then applied for selective cancer cell imaging studies.
Rapidly growing cancer cells have increased levels of intracellular polyamines compared to normal, healthy tissues. Based on the selective reactivity of glycine propargyl esters, probes were ...synthesized that show evidence for selective polyamine reactivity, which was then applied for selective cancer cell imaging studies.
Glycine propargyl ester reactivity shows evidence for selective polyamine reactivity, leading to a new strategy for cancer cell targeting.
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