Synthetic peptide YY analog binds to a cell membrane receptor and deliversfluorescent dye to pancreatic cancer cells

Pancreatic cancer continues to have a dismal prognosis despite multimodalit y treatment plans. Peptide YY (PYY) is a gut hormone that suppresses pancre atic exocrine and endocrine function. Previous experiments have shown that shortened synthetic PYY(22-36) analog decreases pancreatic cancer cell grow th while also decreasing intracellular cyclic adenosine monophosphate. Our purpose was to construct an optimal synthetic PYY analog that binds to panc reatic 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 PW(27-36) were tested with flow cytometry and receptor cross-l inking studies to measure cell membrane binding. Growth inhibition studies were also performed using monotetrazolium tests to determine potency of var ious PYY analogs. Quantitative flow cytometry reveals the highest specific binding of PYY(14-36) to pancreatic cancer cells. Cross-linking studies rev eal a receptor on the cell membrane of human pancreatic ductal adenocarcino ma cells. Growth inhibition studies reveal that PW (14-36) has the highest potency against PANC-1 and MiaPaCa-2 cells. A novel synthetic PYY analog bi nds to the cell surface of pancreatic cancer cells and has the ability to d eliver fluorescent dyes. The strategy of using biotinylated peptides to del iver avidin-dye complexes to cancer cells will allow imaging of pancreatic tumors and delivery of therapeutic agents.