Synthesis and pharmacological properties of a new fluorescent opioid peptide analog

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 (μ, δ and κ) 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 μ opioid receptors that is a δ opioid receptor comparable to biphalin but with an affinity that is over a hundred times lower. This μ, opioid selective fluorescent peptide analog could be applied in pharmacokinetic and pharmacodynamic studies of biphalin related analogs.