| Abstract: |
A synthetic combinatorial library containing 52,128,400 D-amino acid hexapeptides was used to identify a ligand for the opioid receptor. The peptide, Ac-rfwink-NH2 bears no resemblance to any known opioid peptide. Simulations using molecular dynamics, however, showed that three amino acid moieties have the same spatial orientation as the corresponding pharmacophoric groups of the opioid peptide PLO17. Ac-rfwink-NH2 was shown to be a potent agonist at the μ receptor and induced long-lasting analgesia in mice. Analgesia produced by intraperitoneally administered Ac-rfwink-NH2 was blocked by intracerebroventricular administration of naloxone, demonstrating that this peptide may cross the blood-brain barrier. |
| Keywords: |
controlled study; nonhuman; protein conformation; mouse; animal; mice; molecular dynamics; animal experiment; dose-response relationship, drug; central nervous system; simulation; amino acid sequence; molecular sequence data; brain; blood brain barrier; amino acid; models, molecular; rats; pain measurement; analgesics; ligand binding; mu opiate receptor; receptors, opioid, mu; stereoisomerism; naloxone; analgesic activity; opioid peptides; injections, intraventricular; enkephalin, ala(2)-mephe(4)-gly(5)-; opiate peptide; guinea pigs; agonist; male; priority journal; article; endorphins; support, non-u.s. gov't; support, u.s. gov't, p.h.s.; enkephalins; enkephalin, d-penicillamine (2,5)-; hexapeptide; morphiceptin[3 (n methylphenylalanine) 4 dextro prolinamide]
|
