PR4_2009.vp:CorelVentura 7.0 - Institute of Pharmacology

Pharmacological Reports
2009, 61, 727–731
ISSN 1734-1140
Copyright © 2009
by Institute of Pharmacology
Polish Academy of Sciences
Short communication
Synthesis and pharmacological properties of
a new fluorescent opioid peptide analog
Monika Lukowiak1,2, Piotr Kosson1, Wim E. Hennink2,
Andrzej W. Lipkowski1
Medical Research Centre, Polish Academy of Sciences, PL 01-106 Warszawa, Poland
Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht University,
P.O. Box 80082, 3508 TB Utrecht, The Netherlands
Correspondence: Andrzej W. Lipkowski, e-mail: [email protected]
Abstract:
Biphalin, is a palindromic peptide [(Tyr-D-Ala-Gly-Phe-NH-) ] in which two opioid pharmacophores are connected “tail-to-tail.”
This peptide displays a broad affinity for all opioid receptors (m, d and k) 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 m opioid receptors that is a d opioid receptor comparable to biphalin but with an affinity that is over a hundred times lower.
This m opioid selective fluorescent peptide analog could be applied in pharmacokinetic and pharmacodynamic studies of biphalin related analogs.
Key words:
biphalin, opioid receptors, fluorescence
Pharmacological Reports, 2009, 61, 727–731
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