title: Synthesis and pharmacological properties of a new fluorescent opioid peptide analog.
abstract: Biphalin, is a palindromic peptide [(Tyr-D-Ala-Gly-Phe-NH-)2] in which two opioid pharmacophores are connected "tail-to-tail". This peptide displays a broad affinity for all opioid receptors (mu, delta and kappa) as well as exceptionally high antinociceptive activity. Previous structure-activity studies demonstrated that one of the biphalin pharmacophores could be substituted with a hydrophobic group without significant loss of receptor affinity. This paper reports the pharmacological properties of a new analog in which one pharmacophore of biphalin was replaced with fluorescent 7-succinylamido-4-methyl-coumarin. The resulting compound displays an affinity for mu opioid receptors that is a delta opioid receptor comparable to biphalin but with an affinity that is over a hundred times lower. This mu opioid selective fluorescent peptide analog could be applied in pharmacokinetic and pharmacodynamic studies of biphalin related analogs.
authors.affiliation: Medical Research Centre, Polish Academy of Sciences, PL 01-106 Warszawa, Poland.
authors.forename: Monika
authors.initials: M
authors.lastname: Lukowiak
authors.forename: Piotr
authors.initials: P
authors.lastname: Kosson
authors.forename: Wim E
authors.initials: WE
authors.lastname: Hennink
authors.forename: Andrzej W
authors.initials: AW
authors.lastname: Lipkowski
mesh_terms: D000701:Analgesics, Opioid / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D003374:Coumarins / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology; D004151:Dipeptides / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004745:Enkephalins / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology*; D005456:Fluorescent Dyes / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology*; D008297:Male; D018847:Opioid Peptides / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology; D010147:Pain Measurement / Q000187:drug effects / Q000379:methods; D011485:Protein Binding / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017450:Receptors, Opioid, mu / Q000819:agonists / Q000378:metabolism
chemical_list: D000701:Analgesics, Opioid; D003374:Coumarins; D004151:Dipeptides; D004745:Enkephalins; D005456:Fluorescent Dyes; D018847:Opioid Peptides; D017450:Receptors, Opioid, mu; C028744:7-succinylglycyl-prolyl-4-methylcoumaryl-7-amide; C053673:biphalin