[Leu31, Pro34]neuropeptide Y: a specific Y1 receptor agonist.

Abstract

ABSTRACT

The effects of neuropeptide Y and its fragments upon basal and electrically stimulated ion secretion in rat jejunum mucosa

“…Thus loss of amino acids from this region may well result in disruption and unfolding of the molecule thereby further reducing peptide efficacy. Amino acids 11, 12, 13 and 14 form the core sequence holding together the N terminal polyproline helix and amphiphilic a-helix of the C terminal (as shown in Fuhlendorff et al, 1990). Sequential loss of these residues should therefore not greatly alter the tertiary structure of the remaining peptide.…”

Receptor Subtype-specific Docking of Asp6.59 with C-terminal Arginine Residues in Y Receptor Ligands

“…35 ]pNPY were further right-shifted compared with those to pNPY for cells expressing the mutant receptor (Fig. 3) 25 ]NPY/PP were studied in more detail. Indeed, only at Y 2 R and Y 5 R was a 10-fold loss in potency found, whereas Y 1/4 Rs showed wild type properties to these agonists (Fig.…”

“…However, the C-terminal pentapeptide of all natural ligands was identified as an essential region for binding to all YRs (23,24), and these residues of the ligand C terminus seem to represent a core contact domain. Interestingly, studies of analogs containing conformational constraints, when bound at the various YR subtypes, support the concept of structural differences between subtypes in this domain (25)(26)(27)(28). However, the two conserved Arg residues at positions 33 and 35 are important contact sites for all YRs.…”

Modified, cyclic dodecapeptide analog of neuropeptide Y is the smallest full agonist at the human Y2 receptor

“…So the Y~ receptor selectivity of all Pro 3' 1 analogs can be explained [28]. Analogs of Ac-25-36 with replacement of Asn 29, Leu a° or Ile 31 by helix reducing amino acids (Gly, Daa) have been found inactive [29] and large hydrophobic residues active [30].…”