title: Structured cyclic peptides that bind the EH domain of EHD1.
abstract: EHD1 mediates long-loop recycling of many receptors by forming signaling complexes using its EH domain. We report the design and optimization of cyclic peptides as ligands for the EH domain of EHD1. We demonstrate that the improved affinity from cyclization allows fluorescence-based screening applications for EH domain inhibitors. The cyclic peptide is also unusually well-structured in aqueous solution, as demonstrated using nuclear magnetic resonance-based structural models. Because few EH domain inhibitors have been described, these more potent inhibitors will improve our understanding of the roles of EHD1 in the context of cancer invasion and metastasis.
authors.affiliation: Department of Chemistry, Tufts University , 62 Talbot Avenue, Medford, Massachusetts 02155, United States.
authors.forename: Alissa J
authors.initials: AJ
authors.lastname: Kamens
authors.forename: Robyn J
authors.initials: RJ
authors.lastname: Eisert
authors.forename: Tiffany
authors.initials: T
authors.lastname: Corlin
authors.forename: James D
authors.initials: JD
authors.lastname: Baleja
authors.forename: Joshua A
authors.initials: JA
authors.lastname: Kritzer
mesh_terms: D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D010456:Peptides, Cyclic / Q000138:chemical synthesis / Q000737:chemistry*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D013329:Structure-Activity Relationship; D033921:Vesicular Transport Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry*
chemical_list: C120700:EHD1 protein, human; D008024:Ligands; D010456:Peptides, Cyclic; D033921:Vesicular Transport Proteins