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pubmed-article:11287091pubmed:abstractTextNeuropeptide Y (NPY) and pancreatic polypeptide (PP) bind to the Y-receptors with very different affinities: NPY has high affinity for the receptors Y(1), Y(2) and Y(5), while PP binds only to Y(4)-receptor with picomolar affinity. By exchanging of specific amino acid positions between the two peptides, we developed 38 full-length PP/NPY chimeras with binding properties that are completely different from those of the two native ligands. Pig NPY (pNPY) analogs containing the segment 19-23 from human PP (hPP) bound to the Y-receptors with much lower affinity than NPY itself. The affinity of the hPP analog containing the pNPY segments 1-7 and 19-23 was comparable to that of pNPY at the Y(1)- and Y(5)-receptor subtypes, and to that of hPP at the Y(4)-receptor. Furthermore, the presence of the segments 1-7 from chicken PP (cPP) and 19-23 from pNPY within the hPP sequence led to a ligand with IC(50) of 40 pM at the Y(5)-receptor. This is the most potent Y(5)-receptor ligand known so far, with 15-fold higher affinity than NPY.lld:pubmed
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pubmed-article:11287091pubmed:articleTitleY-receptor affinity modulation by the design of pancreatic polypeptide/neuropeptide Y chimera led to Y(5)-receptor ligands with picomolar affinity.lld:pubmed
pubmed-article:11287091pubmed:affiliationDepartment of Applied Bioscience, ETH Zurich, Winterthurerstrasse 190, 8057, Zurich, Switzerland.lld:pubmed
pubmed-article:11287091pubmed:publicationTypeJournal Articlelld:pubmed
pubmed-article:11287091pubmed:publicationTypeResearch Support, Non-U.S. Gov'tlld:pubmed
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