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 language | English |
|---|---|
| Pages (from-to) | 1739-1745 |
| Number of pages | 7 |
| Journal | ChemMedChem |
| Volume | 6 |
| Issue number | 9 |
| DOIs | |
| State | Published - Sep 5 2011 |
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All Science Journal Classification (ASJC) codes
- Pharmacology, Toxicology and Pharmaceutics(all)
- Organic Chemistry
- Molecular Medicine
Cite this
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 journal › Article
}
TY - JOUR
T1 - Unexpected opioid activity profiles of analogues of the novel peptide kappa opioid receptor ligand CJ-15,208
AU - Aldrich, Jane V.
AU - Kulkarni, Santosh S.
AU - Senadheera, Sanjeewa N.
AU - Ross, Nicolette C.
AU - Reilley, Kate J.
AU - Eans, Shainnel O.
AU - Ganno, Michelle L.
AU - Murray, Thomas F.
AU - McLaughlin, Jay P.
PY - 2011/9/5
Y1 - 2011/9/5
N2 - 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.
AB - 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.
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U2 - 10.1002/cmdc.201100113
DO - 10.1002/cmdc.201100113
M3 - Article
VL - 6
SP - 1739
EP - 1745
JO - ChemMedChem
JF - ChemMedChem
SN - 1860-7179
IS - 9
ER -