349545 A Peptoid-Based Targeted Drug Delivery System for the Treatment of Metastatic Cancer
Development of a targeted drug delivery system is a critical step in the effort to improve cancer treatments. Such a system would greatly reduce the harmful side effects of chemotherapy by delivering toxic drugs directly to cancerous cells. Peptoids—synthetic compounds that can be easily produced from readily available amine monomers—have great potential for use in targeted drug delivery. This project aims to develop peptoids that will bind to specific proteins expressed on the surface of cancer cells. These peptoids will be combined into a complex that will bind to the proteins with an even greater affinity than the individual compounds. The peptoid complexes will serve as a targeting system for chemotherapeutic drugs, delivering them directly to cancer cells, thereby preventing healthy tissues from being harmed.
The specific membrane proteins that are being targeted are lectin-like oxidized low-density lipoprotein receptors (LOX-1) and receptors for advanced glycation end-products (RAGE). Both LOX-1 and RAGE are expressed in higher concentrations on cancerous cells than on non-cancerous ones. A combinatorial peptoid library has been created using five side chains that have been identified as being suitable for this application. Each peptoid is six monomers long, resulting in a theoretical library diversity of 15,625 different compounds. A small sample of the library has been screened to identify peptoids with the highest binding affinity for LOX-1. The sequences of ten of the peptoids that displayed high LOX-1 binding affinity are being determined via Edman degradation. These peptoid sequences will be produced on a larger scale and used as the capture elements in protein microarrays to determine their exact binding characteristics with LOX-1. The peptoid sequences will be adjusted as necessary to achieve the desired results.
See more of this Group/Topical: Student Poster Sessions