Synthetic Peptide YY Analog Binds to a Cell Membrane Receptor and Delivers Fluorescent Dye to Pancreatic Cancer Cells

Pancreatic cancer continues to have a dismal prognosis despite multimodality treatment plans. Peptide YY (PYY) is a gut hormone that suppresses pancreatic exocrine and endocrine function. Previous experiments have shown that shortened synthetic PYY(22-36) analog decreases pancreatic cancer cell growth while also decreasing intracellular cyclic adenosine monophosphate. Our purpose was to construct an optimal synthetic PYY analog that binds to pancreatic cancer cells that may be used for imaging and therapy. Biotinylated PYY analogs with lengths ranging from PYY(1-36), PYY(9-36), PYY(14-36), PYY(22-36), and PYY(27-36) were tested with flow cytometry and receptor cross-linking studies to measure cell membrane binding. Growth inhibition studies were also performed using monotetrazolium tests to determine potency of various PYY analogs. Quantitative flow cytometry reveals the highest specific binding of PYY(14-36) to pancreatic cancer cells. Cross-linking studies reveal a receptor on the cell membrane of human pancreatic ductal adenocarcinoma cells. Growth inhibition studies reveal that PYY (14-36) has the highest potency against PANC-1 and MiaPaCa-2 cells. A novel synthetic PYY analog binds to the cell surface of pancreatic cancer cells and has the ability to deliver fluorescent dyes. 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.