Development of a p-Hydroxybenzyl-Alcohol-Linked Glutamate Prodrug for Activation by Pseudomonas Carboxypeptidase G2. Academic Article uri icon

Overview

abstract

  • Directed enzyme-prodrug therapies used for targeted drug delivery require prodrugs that are chemically stable and processed efficiently by the activating enzyme. We recently reported the development of AMS-6-Glu (2), a glutamate-masked version of the cytotoxic natural product 5'-O-sulfamoyladenosine (AMS, 1) that can be activated by Pseudomonas carboxypeptidase G2 (CPG2). Herein, we report the development of a second-generation prodrug, AMS-5'-PHOBA-Glu (5), that undergoes cleavage by CPG2 with >160-fold higher efficiency. Use of a p-hydroxybenzyl alcohol (PHOBA) self-immolative linker overcame unexpected chemical instability observed with a conventional p-aminobenzyl alchohol (PABA) linker.

publication date

  • August 21, 2023

Research

keywords

  • Antineoplastic Agents
  • Prodrugs

Identity

Scopus Document Identifier

  • 85169936635

Digital Object Identifier (DOI)

  • 10.1021/acs.orglett.3c02130

PubMed ID

  • 37602700

Additional Document Info

volume

  • 25

issue

  • 34