A Novel Approach to Prostate Cancer Chemotherapy: Design of Prodrugs for Tissue-Specific Activation
Abstract
During the period supported by this award, we accomplished the synthesis of three of the four protected Linker-Drug conjugates of doxorubicin and 5-fluorouracil (5-FU) proposed in the original application. We determined the stability of two 5-FU Linker-Drug conjugates originally designed and found them to be unstable and not suitable for incorporation into prodrugs. We modified the structure and synthesized two new linkers. The new Linker-Drug conjugates of 5-FU were found to be stable under physiological conditions in the masked form and could undergo once unmasked the cyclization activation process as originally proposed to release the drug 5-FU. We also accomplished the synthesis of a Peptide-Linker-Drug conjugate albeit with an unstable linker. But, the chemistry developed will be useful for the construction of more promising Peptide-Linker-Drug conjugates. Recently, we turned our attention to the synthesis of a Peptide-Linker-Drug conjugate with much less bulky linker. Results are encouraging and will be further investigated.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2002
- Accession Number
- ADB286860
Entities
People
- Longquin Hu
Organizations
- Rutgers University–New Brunswick