Unexpected opioid activity profiles of analogues of the novel peptide kappa opioid receptor ligand CJ-15,208

Jane V. Aldrich, Santosh S. Kulkarni, Sanjeewa N. Senadheera, Nicolette C. Ross, Kate J. Reilley, Shainnel O. Eans, Michelle L. Ganno, Thomas F. Murray, Jay P. McLaughlin

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

An alanine scan was performed on the novel κopioid receptor (KOR) peptide ligand CJ-15,208 to determine which residues contribute to the potent invivo agonist activity observed for the parent peptide. These cyclic tetrapeptides were synthesized by a combination of solid-phase peptide synthesis of the linear precursors, followed by cyclization in solution. Like the parent peptide, each of the analogues exhibited agonist activity and KOR antagonist activity in an antinociceptive assay invivo. Unlike the parent peptide, the agonist activity of the potent analogues was mediated predominantly, if not exclusively, by μopioid receptors (MOR). Thus analogues 2 and 4, in which one of the phenylalanine residues was replaced by alanine, exhibited both potent MOR agonist activity and KOR antagonist activity invivo. These peptides represent novel lead compounds for the development of peptide-based opioid analgesics.

Original languageEnglish
Pages (from-to)1739-1745
Number of pages7
JournalChemMedChem
Volume6
Issue number9
DOIs
StatePublished - Sep 5 2011

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kappa Opioid Receptor
Opioid Analgesics
Ligands
Peptides
Opioid Receptors
Alanine
Solid-Phase Synthesis Techniques
Lead compounds
Cyclization
Phenylalanine
CJ 15,208
Assays

All Science Journal Classification (ASJC) codes

  • Pharmacology, Toxicology and Pharmaceutics(all)
  • Organic Chemistry
  • Molecular Medicine

Cite this

Aldrich, J. V., Kulkarni, S. S., Senadheera, S. N., Ross, N. C., Reilley, K. J., Eans, S. O., ... McLaughlin, J. P. (2011). Unexpected opioid activity profiles of analogues of the novel peptide kappa opioid receptor ligand CJ-15,208. ChemMedChem, 6(9), 1739-1745. https://doi.org/10.1002/cmdc.201100113

Unexpected opioid activity profiles of analogues of the novel peptide kappa opioid receptor ligand CJ-15,208. / Aldrich, Jane V.; Kulkarni, Santosh S.; Senadheera, Sanjeewa N.; Ross, Nicolette C.; Reilley, Kate J.; Eans, Shainnel O.; Ganno, Michelle L.; Murray, Thomas F.; McLaughlin, Jay P.

In: ChemMedChem, Vol. 6, No. 9, 05.09.2011, p. 1739-1745.

Research output: Contribution to journalArticle

Aldrich, JV, Kulkarni, SS, Senadheera, SN, Ross, NC, Reilley, KJ, Eans, SO, Ganno, ML, Murray, TF & McLaughlin, JP 2011, 'Unexpected opioid activity profiles of analogues of the novel peptide kappa opioid receptor ligand CJ-15,208', ChemMedChem, vol. 6, no. 9, pp. 1739-1745. https://doi.org/10.1002/cmdc.201100113
Aldrich JV, Kulkarni SS, Senadheera SN, Ross NC, Reilley KJ, Eans SO et al. Unexpected opioid activity profiles of analogues of the novel peptide kappa opioid receptor ligand CJ-15,208. ChemMedChem. 2011 Sep 5;6(9):1739-1745. https://doi.org/10.1002/cmdc.201100113
Aldrich, Jane V. ; Kulkarni, Santosh S. ; Senadheera, Sanjeewa N. ; Ross, Nicolette C. ; Reilley, Kate J. ; Eans, Shainnel O. ; Ganno, Michelle L. ; Murray, Thomas F. ; McLaughlin, Jay P. / Unexpected opioid activity profiles of analogues of the novel peptide kappa opioid receptor ligand CJ-15,208. In: ChemMedChem. 2011 ; Vol. 6, No. 9. pp. 1739-1745.
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