Synthesis and biological evaluation of pNPY fragments.
Peptide fragments of pNPY corresponding to the C-terminal segments (13-36) and (25-36), the N-terminal segments (1-12) and (1-24), the segments (6-14) and (7-20), which contain a putative beta-turn, and the internal segments (13-24) and (20-30) were synthesized using solid phase methodology. These fragments were assayed for NPY receptor binding activity in the rat hypothalamus membrane preparation, enhancement of food intake in the rat following ivt administration and inhibition of electrically stimulated muscle contraction in the rat vas deferens. Only the C-terminal fragment (13-36) retained some of the activities of pNPY, appearing to act as a weak agonist, having an additive effect with pNPY on the inhibition of muscle contraction and prolonging the duration of action of pNPY in the feeding assay. It also had considerable alpha-helical character, as did pNPY. None of the other peptide fragments had any agonist or antagonist activity. These results suggest that the expression of full biological NPY activity requires both the C- and the N-terminal segments as well as a putative amphiphilic alpha-helical segment (14-31).
Danho
W
W
Exploratory Research, Roche Research Center, Hoffmann-La Roche Inc., Nutley, NJ.
Triscari
J
J
Vincent
G
G
Nakajima
T
T
Taylor
J
J
Kaiser
E T
ET
D000595:Amino Acid Sequence; D000818:Animals; D001066:Appetite / Q000187:drug effects; D001921:Brain / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D002942:Circular Dichroism; D066298:In Vitro Techniques; D007202:Indicators and Reagents; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009478:Neuropeptide Y / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000494:pharmacology; D010446:Peptide Fragments; D011487:Protein Conformation; D051381:Rats; D011919:Rats, Inbred Strains; D017476:Receptors, Neuropeptide Y; D017981:Receptors, Neurotransmitter / Q000378:metabolism; D013329:Structure-Activity Relationship; D014649:Vas Deferens / Q000187:drug effects
D007202:Indicators and Reagents; D009478:Neuropeptide Y; D009842:Oligopeptides; D010446:Peptide Fragments; D017476:Receptors, Neuropeptide Y; D017981:Receptors, Neurotransmitter