Synthesis and Purification of Novel mitoNEET Ligands, Therapeutic Potential for Neurodegenerative Diseases

Riley Kane*, Scott Saylor, and Werner Geldenhuys
Health Sciences Center, West Virginia University, Morgantown, WV 26506

Presentation No.: 80

Assigned Category (Presentation Format): Health Sciences (Poster Presentations)

Student’s Major: Biochemistry

The outer-mitochondrial iron-sulfur [2Fe-2S] protein, mitoNEET, has shown increasing potential as a target for the treatment of neurodegenerative diseases, such as Parkinson’s and Huntington’s disease. Over 1 million Americans suffer from these two conditions each year; with no standard treatment currently in place, alternative receptor biology is being explored. Important regulatory factors involved in these diseases are the conformational changes of mitoNEET protein domains. Although the [2Fe-2S] function has not been isolated, ligand binding at or near this domain has considerable impact on mitochondrial energy transfer. Previous literature concludes that Thiazolidinedione (TZD) derivatives show excellent utility as mitoNEET warheads, and the presence of aromatic rings greatly increase binding affinity towards target domains. As targeting this protein for bioenergetic regulation is relatively unexplored outside of TZD derivatives, our focus for much of this research revolves around the condensation products of phenyl isocyanates/isothiocyanates and amines. While the testing of our compounds is ongoing, this report aims to outline our synthesis and purification methods for potential mitoNEET ligands, as to be used in subsequent in-vivo applications.

Funding: NIH Grant P20GM103434

Program/mechanism supporting research/creative efforts: WVU's SURE program (Rita Rio & Michelle Richards-Babb)