title: Synthesis and characterization of bioactive tamoxifen-conjugated polymers.
abstract: Macromolecular conjugates of tamoxifen could perhaps be used to circumvent some of the limitations of the extensively used breast cancer drug. To test the feasibility of these conjugates, a 4-hydroxytamoxifen analogue was conjugated to a diaminoalkyl linker and then conjugated to activated esters of a poly(methacrylic acid) polymer synthesized by atom transfer radical polymerization. A polymer conjugated to the 4-hydroxytamoxifen analogue with a six-carbon linker showed high affinity for both estrogen receptor alpha and estrogen receptor beta and potent antagonism of the estrogen receptor in cell-based transcriptional reporter assays. These results suggest that the conjugation of 4-hydroxytamoxifen to a polymer results in a macromolecular conjugate that can display ligand in a manner that can be recognized by estrogen receptor and still act as a potent antiestrogen in cells.
authors.affiliation: Department of Medicinal Chemistry and Molecular Pharmacology and Purdue Cancer Center, Purdue University, 575 Stadium Mall Drive, West Lafayette, IN 47907, USA.
authors.forename: Emily L
authors.initials: EL
authors.lastname: Rickert
authors.forename: Joseph P
authors.initials: JP
authors.lastname: Trebley
authors.forename: Anton C
authors.initials: AC
authors.lastname: Peterson
authors.forename: Melinda M
authors.initials: MM
authors.lastname: Morrell
authors.forename: Ross V
authors.initials: RV
authors.lastname: Weatherman
mesh_terms: D002460:Cell Line; D047628:Estrogen Receptor alpha / Q000378:metabolism; D006801:Humans; D015394:Molecular Structure; D011108:Polymers / Q000138:chemical synthesis* / Q000737:chemistry; D013629:Tamoxifen / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D047628:Estrogen Receptor alpha; D011108:Polymers; D013629:Tamoxifen