Prostate Activated Prodrugs and Imaging Agents
Abstract
The goal of this project is to demonstrate that enzymatically active prostate specific antigen (PSA) in the prostatic microenvironment can be used to locally activate either prodrugs or imaging systems. The substrate chosen was a 3 component system composed of a peptide sequence with affinity for PSA, an imaging agent / cytotoxin and a deactivating bridge-linker, which electronically incapacitates the imaging agent. On PSA mediated release, the peptide sequence is designed to uncouple from the bridge which then undergoes spontaneous decomposition, releasing free imaging agent or cytotoxin The linker selected was 4-amino benzyl alcohol and a model substrate [tyrosine] was coupled to the linker and attachment to the clinically used prostatic cancer agent doxorubicin and various imaging agents attempted. Despite numerous attempts, hampered by a combination of chemical instability and incompatible functionality, preparation of desired conjugates was impeded. However, the limiting factors preventing chemical synthesis were uncovered, and the syntheses re-engineered, allowing formation of the first substrate for biological evaluation.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 01, 2003
- Accession Number
- ADA443080
Entities
People
- Graham B. Jones
Organizations
- Northeastern University