A Boronic Acid Conjugate of Angiogenin that Shows ROS-Responsive Neuroprotective Activity

Angew Chem Int Ed Engl. 2017 Mar 1;56(10):2619-2622. doi: 10.1002/anie.201611446. Epub 2017 Jan 25.

Abstract

Angiogenin (ANG) is a human ribonuclease that is compromised in patients with amyotrophic lateral sclerosis (ALS). ANG also promotes neovascularization, and can induce hemorrhage and encourage tumor growth. The causal neurodegeneration of ALS is associated with reactive oxygen species, which are also known to elicit the oxidative cleavage of carbon-boron bonds. We have developed a synthetic boronic acid mask that restrains the ribonucleolytic activity of ANG. The masked ANG does not stimulate endothelial cell proliferation but protects astrocytes from oxidative stress. By differentiating between the two dichotomous biological activities of ANG, this strategy could provide a viable pharmacological approach for the treatment of ALS.

Keywords: amyotrophic lateral sclerosis; angiogenesis; prodrugs; reactive oxygen species; ribonuclease.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyotrophic Lateral Sclerosis / drug therapy*
  • Amyotrophic Lateral Sclerosis / metabolism
  • Amyotrophic Lateral Sclerosis / pathology
  • Boronic Acids / chemistry
  • Boronic Acids / pharmacology*
  • Cell Proliferation / drug effects
  • Humans
  • Neovascularization, Pathologic / drug therapy*
  • Neovascularization, Pathologic / metabolism
  • Neovascularization, Pathologic / pathology
  • Neuroprotective Agents / chemistry
  • Neuroprotective Agents / pharmacology*
  • Oxidative Stress / drug effects
  • Reactive Oxygen Species / metabolism*
  • Ribonuclease, Pancreatic / chemistry
  • Ribonuclease, Pancreatic / pharmacology*

Substances

  • Boronic Acids
  • Neuroprotective Agents
  • Reactive Oxygen Species
  • angiogenin
  • Ribonuclease, Pancreatic