Cholera is an acute diarrheal disease caused by infection in the 
gastrointestinal tract by the gram-negative bacterium, Vibrio cholerae, and is a 
serious public health threat worldwide. There has not been any effective 
treatment for this infectious disease. Cholera toxin (CT), which is secreted by 
V. cholerae, can enter host cells by binding to GM1, a monosialoganglioside 
widely distributed on the plasma membrane surface of various animal epithelial 
cells. The present study was undertaken to generate peptides that are 
conformationally similar to the carbohydrate epitope of GM1 for use in the 
treatment of cholera and related bacterial infection. For this purpose, we used 
cholera toxin B (CTB) subunit to select CTB-binding peptides that structurally 
mimic GM1 from a dodecamer phage-display library. Six GM1-replica peptides were 
selected by biopanning based on CTB recognition. Five of the six peptides showed 
inhibitory activity for GM1 binding to CTB. To test the potential of employing 
the peptide mimics for intervening with the bacterial infection, those peptides 
were examined for their binding capacity, functional inhibitory activity and in 
vitro effects using a human intestinal epithelial cell line, Caco-2 cells. One 
of the peptides, P3 (IPQVWRDWFKLP), was most effective in inhibiting cellular 
uptake of CTB and suppressing CT-stimulated cyclic adenosine monophosphate 
production in the cells. Our results thus provide convincing evidence that 
GM1-replica peptides could serve as novel agents to block CTB binding on 
epithelial cells and prevent the ensuing physiological effects of CT.