Background: Peptidyl α-ketoamides are selective inhibitors of serine and cysteine proteases. Calpains are calcium-dependent proteolytic enzymes, also known as cysteine proteases, which modulate cellular functions. There are 14 independent genes that encode members of the calpain superfamily in humans. Some are confined to specific tissues, while others are ubiquitous. Tissue-specific calpains have gained recent attention and are implicated in several diseases, including diabetes, multiple sclerosis, cancer, cataracts, muscular dystrophy, and Alzheimer’s disease.
Technology: James Powers and Zhao-Zhao Li from the School of Chemistry and Biochemistry at Georgia Tech have designed a novel class of peptidyl α-ketoamide compounds, consisting of a general structure of Cbz-L-Leu-D,L-AA-CONH-R. Their peptidyl α-ketoamides and derivatives contain several different substrate sites, including hydrophobic amino acids, alkyl amino acids, aromatic amino acids, and cationic amino acids. These substrate sites allow these compounds to potently inhibit blood coagulation enzymes or serine proteases. In addition, these novel substrate sites directly inhibit calpains, which are cysteine proteases that play key roles in neurodegenerative diseases and diabetes as well as additional proteolytic enzymes that drive inflammation and cancer.
Potential Commercial Applications: This invention has broad utility and could treat a variety of diseases and disease states, including neurodegenerative disease, diabetes, and cancer. According to the BCC research, the global market for enzyme inhibitors was valued nearly at $104.6 billion in 2010 and was forecasted to reach $127.4 billion by 2016 with a CAGR of 4%.
Benefits / Advantages: