|Title||Fluorescent-labeled bioconjugates of the opioid peptides biphalin and DPDPE incorporating fluorescein-maleimide linkers.|
|Publication Type||Journal Article|
|Year of Publication||2017|
|Authors||Stefanucci A, Lei W, Hruby VJ, Macedonio G, Luisi G, Carradori S, Streicher JM, Mollica A|
|Journal||Future Med Chem|
|Date Published||2017 Jun|
AIM: The conjugation of fluorescent labels to opioid peptides is an extremely challenging task, which needs to be overcome to create new classes of probes for biological assays.
MATERIALS & METHODS: Three opioid peptide analogs of biphalin and [D-Pen2,5]-Enkephalin (DPDPE) containing a fluorescein-maleimide motif were synthesized.
RESULTS & DISCUSSION: The biphalin analog 17 binds to opioid receptors with Ki(μ) = 530 ± 90 nM and Ki(δ) = 69.8 ± 16.4 nM. We then tested the ability of the compounds to stimulate G-protein-coupling, 17 activated μ-receptor expressing cells (EC50 = 16.7 ± 6.7 nM, EMax = 76 ± 4%) as well as δ-receptor expressing cells (EC50 = 42 ± 10 nM, EMax = 34 ± 8%). However, 17 was not able to fluorescently label receptor in live or fixed cells.
CONCLUSION: Our data suggest that the biphalin scaffold could be employed to develop fluorescent ligands with the appropriate fluorescent motif, and suggest a means for further probe development.
|Alternate Journal||Future Med Chem|
Fluorescent-labeled bioconjugates of the opioid peptides biphalin and DPDPE incorporating fluorescein-maleimide linkers.
Faculty Member Reference:
John M. Streicher, PhD