Structure-activity relationships of neuropeptide FF and related peptidic and non-peptidic derivatives.
Neuropeptide FF, a member of the RFamide family of peptides, has demonstrated an interesting array of pharmacological effects. To date however, little information has been obtained as to the exact pharmacological roles of the individual NPFF1 and NPFF2 receptors. Through peptide analogs of NPFF and related peptides, the essential pharmacophore has emerged somewhat. Yet, the field is lacking small molecule ligands selective for each receptor. This review of the structure-activity relationships of the reported NPFF peptide analogs and some non-selective small molecule ligands highlights the current understanding of the pharmacophoric elements required for affinity and activity at the NPFF receptors. The lack of mutagenesis data on the receptor as well as a crystal structure has also hindered the understanding of ligand recognition at the receptor level. If the targets can be further investigated as to their requirements for ligand recognition, the successful development of highly selective ligands should follow.
Laboratory for Applied Drug Design and Synthesis, Department of Medicinal Chemistry, School of Pharmacy, The University of Mississippi, University, MS 38677, USA.
Neha
N
Vyas
Catherine
C
Mollereau
Gwénaël
G
Chevé
Christopher R
CR
McCurdy
D000595:Amino Acid Sequence; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D006801:Humans; D009842:Oligopeptides / Q000502:physiology*; D010446:Peptide Fragments; D018013:Receptors, Neuropeptide / Q000037:antagonists & inhibitors / Q000502:physiology; D013329:Structure-Activity Relationship
C092926:BIBP 3226; D009842:Oligopeptides; D010446:Peptide Fragments; D018013:Receptors, Neuropeptide; C083929:neuropeptide FF receptor; D001120:Arginine; C053651:phenylalanyl-leucyl-phenylalanyl-glutaminyl-prolyl-glutaminyl-arginyl-phenylalaninamide