Tricarboranyl Pentaerythritol-Based Building Block

Mollard, Alexis; Zharov, Ilya

doi:10.1021/ic061297q

Cited by 43 publications

(19 citation statements)

References 41 publications

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“…Our earlier X-ray crystallographic studies of the tricarboranyl pentaerythritol building block indicated that the ester groups in DC-1 are hindered from the nucleophilic attack by the steric bulk of the tricarboranyl pentaerythritol wedge. 66 Similar results, indicating stability of DC-1 , were obtained in DMEM and RPMI-1640 cell culture media.…”

Section: Resultssupporting

confidence: 70%

“… 53 − 55 To date, there have been several reports of multiple polyhedral boranes conjugated to macromolecular scaffolds such as dendrimers, 56 − 65 making this type of chemistry particularly attractive for our purpose. We chose tri- o -carboranyl pentaerythritol, whose synthesis we previously reported, 66 as the building block of our dendritic wedge.…”

Section: Resultsmentioning

confidence: 99%

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Tumor Targeting, Trifunctional Dendritic Wedge

et al. 2014

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We report in vitro and in vivo evaluation of a newly designed trifunctional theranostic agent for targeting solid tumors. This agent combines a dendritic wedge with high boron content for boron neutron capture therapy or boron MRI, a monomethine cyanine dye for visible-light fluorescent imaging, and an integrin ligand for efficient tumor targeting. We report photophysical properties of the new agent, its cellular uptake and in vitro targeting properties. Using live animal imaging and intravital microscopy (IVM) techniques, we observed a rapid accumulation of the agent and its retention for a prolonged period of time (up to 7 days) in fully established animal models of human melanoma and murine mammary adenocarcinoma. This macromolecular theranostic agent can be used for targeted delivery of high boron load into solid tumors for future applications in boron neutron capture therapy.

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Section: Resultssupporting

confidence: 70%

Section: Resultsmentioning

confidence: 99%

Tumor Targeting, Trifunctional Dendritic Wedge

et al. 2014

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“…Tripropargyl ether 4 was prepared in three steps from pentaerythritol according to the procedure described by Zharov 20. The resulting primary alcohol (i.e., 4 ) then reacted with 2‐chloroethyl ether to give 5 ,19 the starting material for the first CuAAC reaction.…”

Section: Resultsmentioning

confidence: 99%

A Convergent Strategy for the Synthesis of Second‐Generation Iminosugar Clusters Using “Clickable” Trivalent Dendrons

et al. 2014

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A convergent strategy to access high‐valency iminosugar clusters based on two successive CuI‐catalysed azide–alkyne cycloadditions is reported. The key step of this approach relies on the grafting of azide‐armed trivalent iminosugar dendrons onto polyalkyne “clickable” scaffolds, thus tripling their initial valency. As a proof of concept, the synthesis of cyclodextrin‐based clusters containing the highest number of peripheral iminosugar ligands reported to date has been achieved. Evaluation of these compounds as mannosidase inhibitors revealed one of the strongest multivalent effects observed so far in glycosidase inhibition.

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“…The same process was repeated for the synthesis of trivalent iminosugars 13 (Scheme ). The tripropargyl ether 11 ,30 prepared in three steps from pentaerythritol, was treated with azide precursors 8 and subsequently deprotected to provide the desired trivalent iminosugars in almost quantitative yields for the two steps. To complete the series, hepta‐ and 14‐valent cyclodextrin‐based iminosugar clusters 2 and 3 were efficiently synthesized by a CuAAC reaction, according to our previously reported strategy,23 as well as monovalent controls 5 that were used to assess the multivalent effect (Scheme ).…”

Section: Resultsmentioning

confidence: 99%

Rescue of Functional CFTR Channels in Cystic Fibrosis: A Dramatic Multivalent Effect Using Iminosugar Cluster‐Based Correctors

et al. 2013

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Cystic fibrosis is caused by a mutation in the gene for the cystic fibrosis transmembrane conductance regulator (CFTR) protein. N-butyl 1-deoxynojirimycin (N-Bu DNJ), a clinical candidate for the treatment of cystic fibrosis, is able to act as a CFTR corrector by overcoming the processing defect of the mutant protein. To explore the potential of multivalency on CFTR correction activity, a library of twelve DNJ click clusters with valencies ranging from 3 to 14 were synthesized. Significantly, the trivalent analogues were found to be up to 225-fold more potent than N-Bu DNJ and up to 1000-fold more potent than the corresponding monovalent models. These results provide the first description of a multivalent effect for correcting protein folding defects in cells and should have application for the treatment of a number of protein folding disorders. Preliminary mechanistic studies indicated that CFTR correction activity enhancement was not due to a multivalent effect in ER-glucosidase inhibition or to a different mode of action of the multivalent iminosugars.

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Tricarboranyl Pentaerythritol-Based Building Block

Cited by 43 publications

References 41 publications

Tumor Targeting, Trifunctional Dendritic Wedge

Tumor Targeting, Trifunctional Dendritic Wedge

A Convergent Strategy for the Synthesis of Second‐Generation Iminosugar Clusters Using “Clickable” Trivalent Dendrons

Rescue of Functional CFTR Channels in Cystic Fibrosis: A Dramatic Multivalent Effect Using Iminosugar Cluster‐Based Correctors

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