title: Synthesis and analgesic activity of alkylated, reduced and constrained oligoheterocyclic peptidomimetic analogs of Leu-enkephalin.
abstract: We report the design and the parallel solid phase synthesis of linear and oligoheterocyclic peptidomimetic analogs of Leu-enkephalin. The described peptidomimetics represent different unique scaffolds that distribute in the space the peptidyl side chains of amino acids essential for biological activity and mimic the bioactive conformation of the Leu-enkephalin peptide. All the compounds were screened in competitive radioligand binding assays to determine their affinities for μ-(MOR), and κ-(KOR) opioid receptors. A reduced analog of Leu-enkephalin TPI1879-26 with activity Ki=60 nM for the mu receptor was identified.
authors.affiliation: Faculty of Sciences of Monastir, Tunisia.
authors.forename: Saoussen
authors.initials: S
authors.lastname: Hammami
authors.affiliation: Faculty of Sciences of Monastir, Tunisia.
authors.forename: Zine
authors.initials: Z
authors.lastname: Mighri
authors.affiliation: Torrey Pines Institute for Molecular Studies, Port Saint Lucie, FL 34987, USA.
authors.forename: Colette T
authors.initials: CT
authors.lastname: Dooley
authors.affiliation: Torrey Pines Institute for Molecular Studies, Port Saint Lucie, FL 34987, USA. Electronic address: adeln@tpims.org.
authors.forename: Adel
authors.initials: A
authors.lastname: Nefzi
mesh_terms: D000478:Alkylation; D000700:Analgesics / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004743:Enkephalin, Leucine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology*; D006571:Heterocyclic Compounds / Q000737:chemistry*; D006801:Humans; D015394:Molecular Structure; D010084:Oxidation-Reduction; D057786:Peptidomimetics / Q000737:chemistry*; D017473:Receptors, Opioid, kappa / Q000037:antagonists & inhibitors*; D017450:Receptors, Opioid, mu / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
chemical_list: D000700:Analgesics; D006571:Heterocyclic Compounds; D057786:Peptidomimetics; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D004743:Enkephalin, Leucine
keywords: Combinatorial chemistry; Oligoheterocyclic peptidomimetics; Opioid receptors; Peptidomimetics; Solid-phase synthesis