title: Synthesis and incorporation into cyclic peptides of tolan amino acids and their hydrogenated congeners: construction of an array of A-B-loop mimetics of the Cε3 domain of human IgE.
abstract: The disruption of the human immunolobulin E-high affinity receptor I (IgE-FcεRI) protein-protein interaction (PPI) is a validated strategy for the development of anti asthma therapeutics. Here, we describe the synthesis of an array of conformationally constrained cyclic peptides based on an epitope of the A-B loop within the Cε3 domain of IgE. The peptides contain various tolan (i.e., 1,2-biarylethyne) amino acids and their fully and partially hydrogenated congeners as conformational constraints. Modest antagonist activity (IC(50) ∼660 μM) is displayed by the peptide containing a 2,2'-tolan, which is the one predicted by molecular modeling to best mimic the conformation of the native A-B loop epitope in IgE.
authors.affiliation: Department of Chemistry, South Kensington Campus, Imperial College, London SW7 2AZ, UK.
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Offermann
authors.forename: John E
authors.initials: JE
authors.lastname: McKendrick
authors.forename: Jimmy J P
authors.initials: JJ
authors.lastname: Sejberg
authors.forename: Bingli
authors.initials: B
authors.lastname: Mo
authors.forename: Mary D
authors.initials: MD
authors.lastname: Holdom
authors.forename: Birgit A
authors.initials: BA
authors.lastname: Helm
authors.forename: Robin J
authors.initials: RJ
authors.lastname: Leatherbarrow
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Beavil
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Sutton
authors.forename: Alan C
authors.initials: AC
authors.lastname: Spivey
mesh_terms: D000596:Amino Acids / Q000138:chemical synthesis* / Q000737:chemistry* / Q000276:immunology; D002942:Circular Dichroism; D000939:Epitopes / Q000737:chemistry* / Q000276:immunology*; D006801:Humans; D006865:Hydrogenation; D007073:Immunoglobulin E / Q000737:chemistry* / Q000276:immunology*; D020128:Inhibitory Concentration 50; D010456:Peptides, Cyclic / Q000138:chemical synthesis* / Q000737:chemistry*; D017455:Receptors, IgE / Q000737:chemistry* / Q000276:immunology*
chemical_list: D000596:Amino Acids; D000939:Epitopes; D010456:Peptides, Cyclic; D017455:Receptors, IgE; D007073:Immunoglobulin E