"Cu, Zn Superoxide Dismutase and ALS: To Charge or Not to Charge?"

Bryan Shaw, PhD
Baylor University

Historically, small molecule drugs have been designed to permute the function of a protein by targeting parameters such as Km, Vmax, Kd, or ∆Gf‡. One parameter—a protein’s net electrostatic charge (Z)—has been categorically overlooked as a medicinal “target”. Can we design drugs to target a protein’s net charge, for example a drug that boosts the net charge of a protein in order to inhibit its amyloidogenesis and cellular permeability? This talk will discuss the rationale and initial testing of this “charge boosting” hypothesis within the context of amyotrophic lateral sclerosis (ALS) that is caused by the self-assembly of Cu, Zn superoxide dismutase (SOD1). At the end of the presentation, a new hypothesis on the chemical etiology of sporadic ALS will also be presented (see Shi, Y., et al., J. Am. Chem. Soc. 2013; 135(42):15897-908).