Article

Self-immolative dendritic probe for direct detection of triacetone triperoxide.

School of Chemistry, Raymond and Beverly Sackler Faculty of Exact Sciences, Tel-Aviv University, Tel Aviv, 69978, Israel.
Chemical Communications (Impact Factor: 6.72). 12/2008; DOI: 10.1039/b814855d
Source: PubMed

ABSTRACT A new self-immolative dendritic probe directly detects triacetone triperoxide through amplification of a single cleavage event initiated by one molecule of hydrogen peroxide into multiple-release of fluorogenic end-groups.

1 Follower
 · 
88 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: Self-immolative dendrimers are uniquely structured molecules that release multiple tail units through a chain fragmentation initiated by a single cleavage at the dendrimer's core. Although bioactivation of self-immolative dendritic molecules with only two reporter groups was demonstrated, enzymatic activation failed for self-immolative dendrimers with more reporters. These large and hydrophobic dendrimers aggregated under aqueous conditions and enzyme did not efficiently trigger chain fragmentation. Here we demonstrate a simple solution to the problem of enzymatic activation of hydrophobic self-immolative dendrimers. The reporter units on the dendritic platform were equipped with ionizable functional group. Polar interactions with water significantly decreased hydrophobicity of the dendrimers and prevented aggregate formation. Consequently, hydrophobic self-immolative dendrons were effectively activated.
    Bioorganic & medicinal chemistry letters 04/2009; 19(14):3959-62. DOI:10.1016/j.bmcl.2009.03.002
  • [Show abstract] [Hide abstract]
    ABSTRACT: Now you bind it--now you don't! Chemical degradation of a dendritic scaffold allows multivalent interactions with DNA to be "switched off" as the multivalent array of ligands breaks down into smaller fragments, offering an approach by which a molecule can be temporarily endowed with high affinity for a biological target--an important concept in the development of new synthetic systems to intervene in biological pathways.
    Angewandte Chemie International Edition 05/2009; 48(22):4047-51. DOI:10.1002/anie.200900401
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The development of targeting approaches to selectively release chemotherapeutic drugs into malignant tissue is a major challenge in anticancer therapy. We have synthesized an N-(2-hydroxypropyl)-methacrylamide (HPMA) copolymer-drug conjugate with an AB(3) self-immolative dendritic linker. HPMA copolymers are known to accumulate selectively in tumors. The water-soluble polymer-drug conjugate was designed to release a triple payload of the hydrophobic drug paclitaxel as a result of cleavage by the endogenous enzyme cathepsin B. The polymer-drug conjugate exhibited enhanced cytotoxicity on murine prostate adenocarcinoma (TRAMP C2) cells in comparison to a classic monomeric drug-polymer conjugate.
    Bioorganic & medicinal chemistry 08/2009; 17(13):4327-35. DOI:10.1016/j.bmc.2009.05.028