Neurolysin is an M3 peptidase family protein that has been shown previously by the inventor to regulate the brain’s response to stroke and its subsequent recovery. As a result, the ability to modulate the activity of neurolysin may pose significant clinical implications for patients suffering from stroke or other neurological disorders.
The disclosed technology describes two separate and independently functional small molecules discovered by the inventor that are effective allosteric enhancers of neurolysin activity. According to the inventor, the disclosed molecules are able to improve the Vmax/Km ratio of neurolysin by as much as 3.7-fold by binding to the hinge region of the neurolysin protein and enhancing enzymatic activity. However, these small molecules demonstrate low potency, indicating their incompatibility with in vivo models. These small molecules may serve as the core components of drug derivatives to treat brain injuries and promote nerve cell repair.
Reference Number: D-1216
Features, Benefits & Advantages:
Enhanced function of neurolysin may improve prognosis for stroke patients.
As a neuropeptidase, neurolysin may play a role in other neurological disorders, broadening the market of applications for the disclosed technology.
The disclosed molecules display high specificity for neurolysin, and do not significantly interfere with the healthy function of similar enzymes.
A U.S. Provisional Patent Application, Serial 62/268,882, was filed on 12/17/2015.
The inventor has successfully shown the enhancement of neurolysin activity by the disclosed small molecules in a quenched fluorescent substrate assay as well as by using three different endogenous substrates of the peptidase. Development of potent derivatives is required to arrive at a pharmaceutically relevant product but will ultimately appeal to a previously unmet need in treatment of brain tissue damage.
Vardan Karamyan, Ph. D., Assistant Professor of Pharmacology, Texas Tech University Health Sciences Center, Amarillo, Texas.
Srinidhi Jayaraman, Graduate Research Student of Pharmacology, Texas Tech University Health Sciences Center, Amarillo, Texas.
David Ostrov, Ph. D., Assistant Professor of Cancer/Genetics, University of Florida, Gainesville, Florida.
Keywords: neurolysin, small molecule, enhancer, activator