title: A Boronic Acid Conjugate of Angiogenin that Shows ROS-Responsive Neuroprotective Activity.
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.
authors.affiliation: Department of Biochemistry, University of Wisconsin-Madison, 433 Babcock Drive, Madison, WI, 53706-1544, USA.
authors.forename: Trish T
authors.initials: TT
authors.lastname: Hoang
authors.affiliation: Department of Chemistry, University of Wisconsin-Madison, 1101 University Avenue, Madison, WI, 53706-1322, USA.
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Smith
authors.affiliation: Department of Biochemistry, University of Wisconsin-Madison, 433 Babcock Drive, Madison, WI, 53706-1544, USA.|Department of Chemistry, University of Wisconsin-Madison, 1101 University Avenue, Madison, WI, 53706-1322, USA.
authors.forename: Ronald T
authors.identifier: 0000-0001-7164-1719
authors.initials: RT
authors.lastname: Raines
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D001897:Boronic Acids / Q000737:chemistry / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D009389:Neovascularization, Pathologic / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000737:chemistry / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012259:Ribonuclease, Pancreatic / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D001897:Boronic Acids; D018696:Neuroprotective Agents; D017382:Reactive Oxygen Species; C046366:angiogenin; D012259:Ribonuclease, Pancreatic
keywords: amyotrophic lateral sclerosis; angiogenesis; prodrugs; reactive oxygen species; ribonuclease