Intracellular delivery of therapeutic proteins through N-terminal site-specific modification

Chem Commun (Camb). 2020 Sep 29;56(77):11473-11476. doi: 10.1039/d0cc04728g.

Abstract

A versatile strategy for the intracellular delivery of functional proteins/antibodies was developed using N-terminal site-specific modification. Adopting orthogonal dual-labeling strategies, a cell-permeable RNase A prodrug was designed complementing N-terminal site-specific modification with lysine labeling. Upon successful cytosolic uptake, the prodrug showed reactive oxygen species (ROS)-dependent targeted cancer therapy.

MeSH terms

  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Drug Delivery Systems*
  • Drug Screening Assays, Antitumor
  • Female
  • HeLa Cells
  • Humans
  • Models, Molecular
  • Molecular Structure
  • Optical Imaging
  • Prodrugs / administration & dosage
  • Prodrugs / chemistry
  • Prodrugs / pharmacology*
  • Reactive Oxygen Species / metabolism
  • Ribonuclease, Pancreatic / chemistry
  • Ribonuclease, Pancreatic / metabolism*
  • Uterine Cervical Neoplasms / drug therapy*
  • Uterine Cervical Neoplasms / metabolism
  • Uterine Cervical Neoplasms / pathology

Substances

  • Antineoplastic Agents
  • Prodrugs
  • Reactive Oxygen Species
  • Ribonuclease, Pancreatic