291933 Targeted Drug Delivery

Monday, October 29, 2012
Hall B (Convention Center )
Hugh Purdy, Ralph E. Martin Department of Chemical Engineering, University of Arkansas, Fayetteville, AR

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 certain proteins expressed on the surface of cancer cells. These peptoids will be combined into a complex that will bind to the specific proteins with an even greater affinity than the individual compounds. The peptoid complexes will serve as carriers 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 much larger amounts 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 affinity for LOX-1. The sequences of these peptoids will be determined via Edman degradation. These peptoid sequences will be produced on a larger scale and used as the capture elements in ELISA microarrays to determine their exact binding characteristics with LOX-1. The sequences will be adjusted as necessary to achieve the desired results.

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