Prodrugs Designed for Enhancing Specificity

Folate-PEG-modified prodmgs of paclitaxel were recently prepared. Although the selected prodrug taxol-7-PEG-folate increased the survival in mice, it was not better than paclitaxel.  

A group from BMS prepared several cathepsin B cleavable dipeptide (Phe-Lys) conjugates through the -aminobenzylcarbonyl linker as prodmgs for paclitaxel and mitomycin C and doxombicin. ° Unformnately, the prodmg did not release the parent dmg in human plasma. 

De Groot et al. reported on the synthesis of tumor-associated protease cleavable prodmgs of paclitaxel. The carbamate and carbonate linkers between 2 -OH of paclitaxel and tripeptides D-Ala-Phe-Lys and D-Val-Leu-Lys were used instead of ester in these prodmgs to avoid nonspecific hydrolysis of 2 -ester by widely 

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