Enzymatic activation of hydrophobic self-immolative dendrimers: the effect of reporters with ionizable functional groups.
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.
Avital-Shmilovici
Michal
M
Department of Organic Chemistry, School of Chemistry, Raymond and Beverly Sackler, Faculty of Exact Sciences, Tel-Aviv University, Tel Aviv, Israel.
Shabat
Doron
D
D050091:Dendrimers / Q000737:chemistry*; D004789:Enzyme Activation; D057927:Hydrophobic and Hydrophilic Interactions; D009579:Nitrobenzoates / Q000737:chemistry; D010399:Penicillin Amidase / Q000378:metabolism*; D011092:Polyethylene Glycols / Q000737:chemistry
D050091:Dendrimers; D009579:Nitrobenzoates; C019251:5-amino-2-nitrobenzoic acid; D011092:Polyethylene Glycols; D010399:Penicillin Amidase