Autohydrolysis of Diglycine-Activated Succinic Esters Boosts Cellular Uptake

Overview

Journal Angew Chem Int Ed Engl

Specialty Chemistry

Date 2023 Jul 19

PMID 37468437

Authors

Jiaqi Guo

Weiyi Tan

Hongjian He

Bing Xu

Affiliations

Soon will be listed here.

Abstract

Rapid cellular uptake of synthetic molecules remains a challenge, and the motif frequently employed to generate prodrugs, succinic ester, unfortunately lowers the efficacy of the desired drugs due to their slow ester hydrolysis and low cell entry. Here we show that succinic ester-containing diglycine drastically boosts the cellular uptake of supramolecular assemblies or prodrugs. Specifically, autohydrolysis of the diglycine-activated succinic esters turns the nanofibers of the conjugates of succinic ester and self-assembling motif into nanoparticles for fast cellular uptake. The autohydrolysis of diglycine-activated succinic esters and drug conjugates also restores the efficacy of the drugs. 2D nuclear magnetic resonance (NMR) suggests that a "U-turn" of diglycine favors intramolecular hydrolysis of diglycine-activated succinic esters to promote autohydrolysis. As an example of rapid autohydrolysis of diglycine-activated succinic esters for instant cellular uptake, this work illustrates a nonenzymatic bond cleavage approach to develop effective therapeutics for intracellular targeting.

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