Design of inhibitors for matrix metalloproteinases

Matrix metalloproteinases are a family of enzymes whose malfunction has been implicated in variable diseases including arthritis, osteoporosis, ALS, Alzheimer’s disease, and cancer. The function of some MMPs is associated with the most aggressive types of cancer and directly promotes metastasis. However, only some of MMP family members play role in disease progression, while others are essential and/or play therapeutic role. Thus, all non-specific MMP inhibitors proved to be highly toxic and could not be used as drugs. We have developed a pioneering strategy for designing highly specific inhibitors of each MMP type using a combination of computational design and experimental protein engineering. Our MMP inhibitors are based on a small protein, TIMP2, that has been engineered to possess high affinity and high specificity towards each MMP family member. Our engineered proteins possess high potential to become future drugs for cancer and other diseases.