Abstracts
2000 Digestive Disease Week

# 2453 Synthetic Peptide YY Analog Binds to a 68 kD Cell Membrane Receptor and Delivers Fluorescent Dye for Imaging and Therapeutic Treatment of Human Pancreatic Cancers.
Carson D. Liu, David Kwan, Natalie Simon, David W. McFadden, Los Angeles, CA

We have previously shown that PYY(22-36) decreases pancreatic cancer growth while also decreasing intracellular cyclic AMP. Our purpose is to construct an optimal synthetic PYY analog that binds to pancreatic cells and may be used for therapy and imaging. Methods: Biotinylated PYY analogs with lengths ranging from PYY(1-36), PYY(14-36), PYY(22-36), PYY(27-36), and NPY(3-36)were tested with flow cytometry and receptor cross linking studies to measure specific cell membrane binding. Growth inhibition studies were also performed by MTT studies to determine potency of various PYY analogs. PANC-1, MiaPaCa-2(Pancreatic Ductal Adenocarcinoma Cells), AR42J(Pancreatic Acinar Cell), 3T3(Fibroblast cells) were used in receptor binding and growth inhibition studies. Results: Quantiative flow cytometry revealed specific binding of PYY(14- 36) to pancreatic cancer cells. Cross linking studies reveal a receptor of 68 kD on the cell surface of ductal adenocarcinoma cell lines. Fluorescent microscopy confirms binding of peptides to cell surfaces. Growth inhibition studies were performed after a 24 hour treatment period to biotinylated PYY(14-36). Results are shown in table below. Conclusion: We are describing a novel synthetic PYY analog that has the ability to deliver fluorescent dyes and decrease pancreatic cancer cell growth. The strategy of using biotinylated peptides to deliver avidin-dye complexes to cancer cells will allow imaging of pancreatic tumors and delivery of therapeutic agents. A 68 kD receptor exists on pancreatic ductal adenocarcinoma cells allowing binding of PYY(14-36) while native PYY does not bind to cells.