Synthesis and characterization of bioactive tamoxifen-conjugated polymers.
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.
Rickert
Emily L
EL
Department of Medicinal Chemistry and Molecular Pharmacology and Purdue Cancer Center, Purdue University, 575 Stadium Mall Drive, West Lafayette, IN 47907, USA.
Trebley
Joseph P
JP
Peterson
Anton C
AC
Morrell
Melinda M
MM
Weatherman
Ross V
RV
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*
D047628:Estrogen Receptor alpha; D011108:Polymers; D013629:Tamoxifen