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Peptide phage display is a method by which up to 1 billion different peptides can be screened for binding to cancer cells or other targets of interest. The Frangioni Laboratory has developed the mJ1 phage display vector, as well as an integrated family of shuttle vectors, which permit phage-derived peptides to be displayed as fusions to secreted placental alkaline phosphatase, sub-cellular targeted green fluorescent proteins, or the Gal4 DNA binding domain. We have also developed a series of constrained peptide libraries and are actively screening them against cancer cells of interest.
A new program in the Frangioni Laboratory is focused on combinatorial chemistry and small molecule screening. Details of this effort will be presented in the near future.
Many previously described molecules, such as enzyme inhibitors and therapeutics, can be re-engineered for use as contrast agents. Our successes to date include Pam78, a near-infrared fluorescent pamidronate derivative that can be used to find breast cancer microcalcification, osteoblastic metastses, and the calcification of atherosclerosis, and GPI 11254-36, a small molecule targeting the active site of prostate specific membrane antigen (PSMA). Both compounds serve as "modular" ligands that can be conjugated to a variety of contrast agents and therapeutics.
