Highly potent fluorescent analogues of the opioid peptide [Dmt1] DALDA.
H-Dmt-D-Arg-Phe-Lys-NH2 (Dmt=2',6'-dimethyltyrosine) ([Dmt1] DALDA) is a highly potent and selective micro opioid peptide agonist capable of producing an antinociceptive effect after systemic administration. Fluorescent analogues of [Dmt1] DALDA containing either beta-dansyl-L-alpha,beta-diaminopropionic acid [Dap(dns)] or beta-anthraniloyl-L-alpha,beta-diaminopropionic acid [Dap(atn)] in place of Lys4 were synthesized. Both analogues retained subnanomolar mu opioid receptor binding affinity, very high mu opioid agonist activity in the guinea pig ileum assay and extraordinarily high antinociceptive activity in the mouse tail-flick test (intrathecal administration). The maxima of the fluorescence emission spectra recorded in Tris-HCl buffer (pH 6.6) indicated a completely aqueous environment of the fluorophore in both peptides. The high fluorescence quantum yield (phi=0.358) of the [Dap(atn)4] analogue was particularly remarkable. These fluorescent [Dmt1] DALDA analogues represent valuable pharmacological tools for various applications, including studies on the binding to receptors and other biopolymers, cellular uptake and intracellular distribution, and tissue distribution.
Berezowska
Irena
I
Laboratory of Chemical Biology and Peptide Research, Clinical Research Institute of Montreal, 110 Pine Avenue West, Montreal, Quebec, Canada H2W 1R7.
Chung
Nga N
NN
Lemieux
Carole
C
Zelent
Bogumil
B
Szeto
Hazel H
HH
Schiller
Peter W
PW
D000818:Animals; D006224:Cricetinae; D005453:Fluorescence; D006168:Guinea Pigs; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D011422:Propionates / Q000378:metabolism; D017450:Receptors, Opioid, mu / Q000819:agonists* / Q000378:metabolism; D013050:Spectrometry, Fluorescence; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000378:metabolism*
D009842:Oligopeptides; D011422:Propionates; D017450:Receptors, Opioid, mu; C063076:tyrosyl-arginyl-phenylalanyl-lysinamide; C076121:2',6'-dimethyltyrosine; D014443:Tyrosine