PMID: 9437724Jan 1, 1997Paper

Structural modifications of the N-terminal tetrapeptide segment of [D-Ala2]deltorphin I: effects on opioid receptor affinities and activities in vitro and on antinociceptive potency

Peptides
R SchmidtP W Schiller

Abstract

A series of deltorphin I analogs containing D- or L-N-methylalanine (MeAla), D- or L-proline (Pro), alpha-aminoisobutyric acid (Aib), sarcosine (Sar) or D-tert-leucine (Tle) in place of D-Ala2, or phenylalanine in place of Tyr1, was synthesized. The opioid activity profiles of these peptides were determined in mu and delta opioid receptor-representative binding assays and bioassays in vitro as well as in the rat tail flick test in vivo. In comparison with the deltorphin I parent, both the L- and the D-MeAla2-analog were slightly more potent delta agonists in the mouse vas deferens (MDV) assay, and the D-MeAla2-analog showed two-fold higher antinociceptive potency in the analgesic test. In view of the fact that deltorphin analogs with an unsubstituted L-amino acid residue in the 2-position generally lack opioid activity, the observed high delta opioid potency of [L-MeAla2]deltorphin I is postulated to be due to the demonstrated presence of a conformer with a cis Tyr1-MeAla2 peptide bond, since the cis conformer allows for a spatial arrangement of the pharmacophoric moieties in the N-terminal tripeptide segment similar to that in active deltorphin analogs containing a D-amino acid residue in the 2-position. Substitution of Aib in...Continue Reading

References

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Citations

May 27, 2003·Biopolymers·Sharon D BryantLawrence H Lazarus
Jun 29, 2002·Life Sciences·Rocío GirónNadine Jagerovic
Mar 12, 2003·Bioorganic & Medicinal Chemistry·Christophe DardonvilleMa Isabel Martín
Feb 6, 2004·Biological & Pharmaceutical Bulletin·Yusuke SasakiAkihiro Ambo
Jan 1, 2012·International Journal of Medicinal Chemistry·Yusuke Sasaki, Akihiro Ambo
Mar 5, 2004·The Journal of Biological Chemistry·Ibtihal FadhilKatharine A Carpenter
Mar 18, 1999·Progress in Neurobiology·L H LazarusS Salvadori

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