title: Design, synthesis, and characterization of fatty acid derivatives of a dimeric peptide-based postsynaptic density-95 (PSD-95) inhibitor.
abstract: Dimeric peptide-based inhibitors of postsynaptic density-95 (PSD-95) can reduce ischemic brain damage and inflammatory pain in rodents. To modify the pharmacokinetic profile, we designed a series of fatty acid linked dimeric ligands, which potently inhibits PSD-95 and shows improved in vitro blood plasma stability. Subcutaneous administration in rats showed extended stability and sustained release of these ligands. This can facilitate new pharmacological uses of PSD-95 inhibitors and further exploration of PSD-95 as a drug target.
authors.affiliation: Department of Drug Design and Pharmacology, University of Copenhagen , Universitetsparken 2, DK-2100 Copenhagen, Denmark.
authors.forename: Klaus B
authors.initials: KB
authors.lastname: Nissen
authors.forename: Julie J
authors.initials: JJ
authors.lastname: Andersen
authors.forename: Linda M
authors.initials: LM
authors.lastname: Haugaard-Kedström
authors.forename: Anders
authors.initials: A
authors.lastname: Bach
authors.forename: Kristian
authors.initials: K
authors.lastname: Strømgaard
mesh_terms: D000818:Animals; D000076122:Disks Large Homolog 4 Protein; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D005227:Fatty Acids / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors*; D008024:Ligands; D008565:Membrane Proteins / Q000037:antagonists & inhibitors*; D015394:Molecular Structure; D010455:Peptides / Q000737:chemistry*; D051381:Rats; D013329:Structure-Activity Relationship
chemical_list: D000076122:Disks Large Homolog 4 Protein; C501449:Dlg4 protein, rat; D005227:Fatty Acids; D047908:Intracellular Signaling Peptides and Proteins; D008024:Ligands; D008565:Membrane Proteins; D010455:Peptides