Targeted Therpeutics for Prostate Cancer, Behind the Scenes of PSMA & Cysteine Protease Trapping Mechanism

Author

Alireza Basiri, University of Nebraska Medical CenterFollow

Graduation Date

Fall 12-16-2022

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Programs

Pharmaceutical Sciences

First Advisor

Jered Garrison, PhD

Second Advisor

Corey Hopkins, PhD

Third Advisor

Dong Wang, PhD

Fourth Advisor

Kaustubh Datta, PhD

Abstract

In an attempt to increase the residence time of PSMA-targeted theranostics inside the prostate cancer cells and tumors, we designed and prepared a CPTA-PSMATA resembling PSMA-617 by adding a well-known cysteine protease inhibitor (E-64) to the conjugate. Lysosomal proteases, including cysteine, serine, and aspartic families of hydrolytic enzymes, are expressed in high concentrations in the lysosomes and are responsible for the catabolism of proteins inside the cell [165, 278]. We proposed that after successful internalization of the PSMA-targeted conjugates into the cells, they will be conveyed to the endolysosomes. In these endolysosomal compartments, the E-64 moiety will covalently bind to cysteine proteases such as cysteine cathepsins, thereby forming high molecular weight conjugates.

Comments

2022 Copyright, the authors

Recommended Citation

Basiri, Alireza, "Targeted Therpeutics for Prostate Cancer, Behind the Scenes of PSMA & Cysteine Protease Trapping Mechanism" (2022). Theses & Dissertations. 711.
https://digitalcommons.unmc.edu/etd/711