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Structure- and conformation-activity studies of nociceptin/orphanin FQ receptor dimeric ligands

View Article: PubMed Central - PubMed

ABSTRACT

The peptide nociceptin/orphanin FQ (N/OFQ) and the N/OFQ receptor (NOP) constitute a neuropeptidergic system that modulates various biological functions and is currently targeted for the generation of innovative drugs. In the present study dimeric NOP receptor ligands with spacers of different lengths were generated using both peptide and non-peptide pharmacophores. The novel compounds (12 peptide and 7 nonpeptide ligands) were pharmacologically investigated in a calcium mobilization assay and in the mouse vas deferens bioassay. Both structure- and conformation-activity studies were performed. Results demonstrated that dimerization did not modify the pharmacological activity of both peptide and non-peptide pharmacophores. Moreover, when dimeric compounds were obtained with low potency peptide pharmacophores, dimerization recovered ligand potency. This effect depends on the doubling of the C-terminal address sequence rather than the presence of an additional N-terminal message sequence or modifications of peptide conformation.

No MeSH data available.


CD spectra of peptide N/OQF(1–13) (black line), peptide 10 (red line), peptide 11 (green line), peptide 15 (blue line) in SDS micelle solution.
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f4: CD spectra of peptide N/OQF(1–13) (black line), peptide 10 (red line), peptide 11 (green line), peptide 15 (blue line) in SDS micelle solution.

Mentions: Monomeric compounds N/OFQ(1-13)-NH2, and 10, and dimeric compounds 11, 15 were investigated by CD spectroscopy in sodium dodecylsulphate (SDS) micelle solution (Fig. 4). CD spectra of compounds N/OFQ(1-13)-NH2, 10 and 11 are very similar. Minima at 205 and 227 nm, and maximum at 193 nm are indicative of helical structure and minimum at 205 is also typical of turns.


Structure- and conformation-activity studies of nociceptin/orphanin FQ receptor dimeric ligands
CD spectra of peptide N/OQF(1–13) (black line), peptide 10 (red line), peptide 11 (green line), peptide 15 (blue line) in SDS micelle solution.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5382891&req=5

f4: CD spectra of peptide N/OQF(1–13) (black line), peptide 10 (red line), peptide 11 (green line), peptide 15 (blue line) in SDS micelle solution.
Mentions: Monomeric compounds N/OFQ(1-13)-NH2, and 10, and dimeric compounds 11, 15 were investigated by CD spectroscopy in sodium dodecylsulphate (SDS) micelle solution (Fig. 4). CD spectra of compounds N/OFQ(1-13)-NH2, 10 and 11 are very similar. Minima at 205 and 227 nm, and maximum at 193 nm are indicative of helical structure and minimum at 205 is also typical of turns.

View Article: PubMed Central - PubMed

ABSTRACT

The peptide nociceptin/orphanin FQ (N/OFQ) and the N/OFQ receptor (NOP) constitute a neuropeptidergic system that modulates various biological functions and is currently targeted for the generation of innovative drugs. In the present study dimeric NOP receptor ligands with spacers of different lengths were generated using both peptide and non-peptide pharmacophores. The novel compounds (12 peptide and 7 nonpeptide ligands) were pharmacologically investigated in a calcium mobilization assay and in the mouse vas deferens bioassay. Both structure- and conformation-activity studies were performed. Results demonstrated that dimerization did not modify the pharmacological activity of both peptide and non-peptide pharmacophores. Moreover, when dimeric compounds were obtained with low potency peptide pharmacophores, dimerization recovered ligand potency. This effect depends on the doubling of the C-terminal address sequence rather than the presence of an additional N-terminal message sequence or modifications of peptide conformation.

No MeSH data available.