Journal
JOURNAL OF LIPID RESEARCH
Volume 46, Issue 7, Pages 1512-1516Publisher
ELSEVIER
DOI: 10.1194/jlr.M500048-JLR200
Keywords
sequential elution; obesity; peptide drug leads
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Interference with fat hydrolysis results in the reduced use of ingested lipids. Inhibition of pancreatic lipase reduces the efficiency of fat absorption in the small intestine and thereby initiates modest long-term reduction in body weight. In an attempt to select peptides with affinity for the surface of pancreatic lipase and potential inhibitory activity, a random, cyclic heptapeptide phage-displayed library was used. Five independent selections, differing in elution step, were performed. In three selection protocols, a sequential elution strategy was applied in anticipation of improving the selection of high-affinity clones. Four heptapeptides with the highest affinity, seemingly for pancreatic lipase, were selected, synthesized, and characterized for their capacity to inhibit enzyme function. Although no clear consensus among the sequenced peptides was found, one of the selected peptides inhibited pancreatic lipase with an apparent inhibition constant of 16 mu M.-Lunder, M., T. Bratkovic, S. Kreft, and B. Strukelj. Peptide inhibitor of pancreatic lipase selected by phage display using different elution strategies.
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