title: Modulation of human estrogen receptor α activity by multivalent estradiol-peptidomimetic conjugates.
abstract: Estradiol-peptidomimetic conjugates (EPCs) are linear, sequence-specific peptoid oligomers that site-specifically display multiple copies of 17β-estradiol (E2), a ligand for the human estrogen receptor α (hERα). We evaluate the ability of multivalent EPCs to activate hERα-mediated transcription. EPCs activated the hERα in both a length- and valence-dependent manner, with the highest levels of activation generated by divalent peptoid 6-mers, divalent 18-mers, and trivalent 9-mers. Hexavalent EPCs did not activate hERα, but instead blocked E2-mediated hERα activation. The physicochemical features of EPCs can be precisely tuned, which may allow the generation of a library of chemical tools for modulating specific effects of estrogens.
authors.affiliation: Department of Chemistry, New York University, 100 Washington Square East, New York, New York 10003, USA.
authors.forename: Justin M
authors.initials: JM
authors.lastname: Holub
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Garabedian
authors.forename: Kent
authors.initials: K
authors.lastname: Kirshenbaum
mesh_terms: D002460:Cell Line; D002463:Cell Membrane Permeability; D004958:Estradiol / Q000737:chemistry / Q000494:pharmacology*; D047628:Estrogen Receptor alpha / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D005456:Fluorescent Dyes / Q000138:chemical synthesis; D006801:Humans; D006868:Hydrolysis; D018716:Molecular Mimicry; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology*; D014158:Transcription, Genetic / Q000502:physiology
chemical_list: D047628:Estrogen Receptor alpha; D005456:Fluorescent Dyes; D010455:Peptides; D004958:Estradiol