title: Novel design of bicyclic beta-turn dipeptides on solid-phase supports and synthesis of [3.3.0]-Bicyclo([2,3])-leu-enkephalin analogues.
abstract: [structure: see text] External bicyclic beta-turn dipeptide mimetics provide an excellent design approach that can offer a rich chiral ensemble of structures with different backbone conformations. We report herein a novel design of a convergent combinatorial synthetic methodology, which is illustrated by the solid-phase synthesis of a series of [3.3.0]-bicyclo([2,3])-Leu-enkephalin analogues. The reactions were optimized and the epimeric configurations were determined by 2D NMR spectroscopy. Biological assays show that these analogues have more potent delta binding affinity and bioactivity for delta vs micro opioid receptor, which may be related to the different conformations preferred by these analogues in our modeling studies.
authors.affiliation: Department of Chemistry, University of Arizona, 1306 East University Boulevard, Tucson, Arizona 85721, USA.
authors.forename: Xuyuan
authors.initials: X
authors.lastname: Gu
authors.forename: Jinfa
authors.initials: J
authors.lastname: Ying
authors.forename: Richard S
authors.initials: RS
authors.lastname: Agnes
authors.forename: Edita
authors.initials: E
authors.lastname: Navratilova
authors.forename: Peg
authors.initials: P
authors.lastname: Davis
authors.forename: Gannon
authors.initials: G
authors.lastname: Stahl
authors.forename: Frank
authors.initials: F
authors.lastname: Porreca
authors.forename: Henry I
authors.initials: HI
authors.lastname: Yamamura
authors.forename: Victor J
authors.initials: VJ
authors.lastname: Hruby
mesh_terms: D004151:Dipeptides / Q000138:chemical synthesis* / Q000494:pharmacology; D015195:Drug Design; D004743:Enkephalin, Leucine / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology; D008958:Models, Molecular; D018716:Molecular Mimicry; D015394:Molecular Structure; D017433:Protein Structure, Secondary; D017465:Receptors, Opioid, delta / Q000378:metabolism; D017450:Receptors, Opioid, mu / Q000378:metabolism; D013237:Stereoisomerism
chemical_list: D004151:Dipeptides; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu; D004743:Enkephalin, Leucine