National Cancer Research Institute South of England
Prostate Cancer Collaborative


Optimisation of linkers in a polymeric prodrug system for selective prostate delivery of drugs


Dr Michael Threadgill

University of Bath

The overall aim of the prostate cancer research programme at Bath is to develop a novel polymeric prodrug to release doxorubicin selectively in prostate tumours through an innovative system. This system can also deliver other cytotoxins selectively.

We are seeking to design two levels of selectivity into this polymeric prodrug. Firstly, the polymer-drug conjugate should be selectively retained in solid tumours through the enhanced permeation and retention (EPR) effect. Secondly, the drug is designed to be released from the polymer carrier by the action of prostate-specific antigen (PSA), which is enzymically active as a peptidase only in the prostate. PSA is active extracellularly in the prostate and should cleave the short peptide sequence linking the drug to the polymer.

However, PSA is an endopeptidase and it is necessary to include a dipeptide-like "molecular clip" between the recognition sequence (SSKLQ) and the drug to promote efficient release of drug without any residual amino-acids remaining attached to the drug.

  The specific objectives of this short project are (i) to optimise the self-immolative aminoacyl-dimethylthiaproline "molecular clip", which, after release from the polymer by PSA, will liberate free drug; (ii)  to evaluate drug release from an advanced model com­pris­ing the PSA-cleavable peptide joined to the drug by the molecular clip.


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Aetiology and Genetics

Epidemiological Identification of Families
Genetic Susceptibility
Diet and Environment

Molecular Pathology

Links to Cancer Genome Project
Development of Normal Prostate
Microarray Expression Profiling
Candidate Genes
Novel Telomerase Suppressor Genes
Subtractive Hybridization

Novel Therapies

New Drugs for Prostate Cancer
Intensity Modulated Radiotherapy
Academic Urology Unit
Novel Targets from Cancer Genome Project
Novel Mechanism Based Drugs

Core Resources

Cancer Gene Cloning Lab
Prostate Tissue arrays
Microarray laboratory
Tissue and blood collections

Pilot and Development Funds

Tumor micro-environment in early prostate cancer

Meetings and Seminars

Contact us on Email: Tel: 0208 643 8901 Fax: 0208 770 7290 This page last modified: 25/11/04