Targeted delivery of a therapeutic payload to prostate tumours
Lead Research Organisation:
University of Strathclyde
Department Name: Pure and Applied Chemistry
Abstract
To develop an understanding of the cell penetrating ability of cell penetrating peptides (CPP) by Synthesis, characterisation and biological testing of various CPP. The aim is to obtain a structure activity relationship between the CPP and their cellular permeability. Use these compounds as delivery vehicles for prostate cancer tumours via targeting ligand for prostate specific membrane antigen (PSMA)
Studentship Projects
| Project Reference | Relationship | Related To | Start | End | Student Name |
|---|---|---|---|---|---|
| EP/P51066X/1 | 01/10/2016 | 30/09/2021 | |||
| 1858461 | Studentship | EP/P51066X/1 | 01/10/2016 | 31/01/2021 | Jack Robertson |
| Description | First we have developed a new set of conditions to synthesise amino acid analogues (amidines and guanidines). We aim to apply this analogue strategy to cell penetrating peptides (CPPs). We have discovered a limit to some CPPs (Tat peptide for example) in delivering certain cargos to androgen sensitive prostate cancer cell lines. We have found a peptide that is also more toxic to androgen sensitive prostate cancer cells than enzalutamide and docetaxol. This work has now led to collaboration with professor Matthew Wood (University of Oxford) and Dr Allan Watson (University of St Andrews). Building upon this we have identified alternative CPPs to Tat for delivery of a small fluorophore and aim to use these CPPs to deliver larger therapeutics. Along side this work we have synthesised a series of analogues of the anti-parasitic drug pentamidine (Using amidine conditions developed for amino acid analogues). These analogues show reasonable activity against the parasite (Trypanosoma brucei) and we are seeking to use this chemistry to develop a new fluorescent probe to follow pentamidine within the parasite. This has also led to a further collaboration with Professor Micheal Barret (University of Glasgow) |
| Exploitation Route | Synthetic procedures can be applied to other chemical species besides amino acids, possible pharmaceutical/medicinal compound applications. Initial findings with cell penetrating peptides could be used to design alternative assays to measure cell penetration. The use of a new probe to study the therapeutic activity of pentamidine and gain a better understanding of the parasite causing the disease. |
| Sectors | Chemicals,Pharmaceuticals and Medical Biotechnology |