title: Synthetic routes to the Neuropeptide Y Y1 receptor antagonist 1229U91 and related analogues for SAR studies and cell-based imaging.
abstract: The potent Y1 receptor antagonist, 1229U91 has an unusual cyclic dimer structure that makes syntheses of analogue series quite challenging. We have examined three new routes to the synthesis of such peptides that has given access to novel structural variants including heterodimeric compounds, ring size variants and labelled conjugates. These compounds, including a fluorescently labelled analogue VIII show potent antagonism that can be utilised in studying Y1 receptor pharmacology.
authors.affiliation: Medicinal Chemistry, Monash Institute of Pharmaceutical Sciences, 381 Royal Parade, Parkville, VIC 3052, Australia. philip.thompson@monash.edu.
authors.forename: Simon J
authors.initials: SJ
authors.lastname: Mountford
authors.forename: Mengjie
authors.initials: M
authors.lastname: Liu
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.forename: Marleen
authors.initials: M
authors.lastname: Groenen
authors.forename: Herbert
authors.initials: H
authors.lastname: Herzog
authors.forename: Nicholas D
authors.initials: ND
authors.lastname: Holliday
authors.forename: Philip E
authors.initials: PE
authors.lastname: Thompson
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002625:Chemistry, Organic / Q000379:methods*; D002851:Chromatography, High Pressure Liquid; D003500:Cyclization; D005453:Fluorescence; D049452:Green Fluorescent Proteins / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D008024:Ligands; D051379:Mice; D057054:Molecular Imaging; D008969:Molecular Sequence Data; D010456:Peptides, Cyclic / Q000138:chemical synthesis* / Q000737:chemistry; D051381:Rats; D017476:Receptors, Neuropeptide Y / Q000819:agonists* / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship; D014162:Transfection
chemical_list: C097287:1229U91; D008024:Ligands; D010456:Peptides, Cyclic; D017476:Receptors, Neuropeptide Y; C097212:neuropeptide Y-Y1 receptor; D049452:Green Fluorescent Proteins