Syntheses and receptor affinities of partial sequences of peptide YY (PYY)

Peptide YY (PYY) is a 36 residue peptide amide isolated from porcine intestine. It has distinct structural homology with neuropeptide Y (NPY) and pancreatic polypeptide (PP). Endocrine cells of pancreas and gut of mammals have been shown to contain PYY-like immunoreactivity. PYY exhibits both NPY- and PP-like biological activities such as inhibition of exocrine pancreatic secretion, stimulation of feeding, vasoconstriction and inhibition of intestinal motility. PYY has also been shown to be a potent inhibitor of intestinal fluid and electrolyte secretion. Although PYY-preferring receptors have been identified and characterized in rat jejunal epithelium, no structure-activity studies with PYY and receptors have been reported. We therefore synthesized a number of partial sequences of PYY and evaluated their binding relative to the intact hormone in a radioreceptor assay. This investigation has resulted in identifying the receptor binding region of PYY. This information may prove useful in designing agonistic and antagonistic peptides not only for PYY but also for other structurally related hormones such as NPY.