Facile synthesis of cids: biotinylated estrone oximes efficiently heterodimerize estrogen receptor and streptavidin proteins in yeast three hybrid systems.
[structure: see text] We synthesized estrone oximes as chemical inducers of protein heterodimerization (CIDs). Estrone-17-(O-carboxymethyl)oxime coupled to biotinamidocaproic acid via N,N'-dimethylhexane-1,6-diamine efficiently heterodimerizes estrogen receptors (ERs) and streptavidin Y43A in yeast three hybrid systems, activating gene expression over 100-fold at 10 microM. Related hexane-1,6-diamine and estradiol-6-(O-carboxymethyl)oxime derivatives were ineffective CIDs due to low affinity for ERs when bound to streptavidin. Estrone oximes bind ERs with submicromolar affinity and effectively display small molecules to target proteins expressed in yeast.
Muddana
Smita S
SS
Department of Chemistry, The Pennsylvania State University, University Park, Pennsylvania 16802, USA.
Peterson
Blake R
BR
D019921:Biotinylation; D019281:Dimerization; D004305:Dose-Response Relationship, Drug; D004970:Estrone / Q000138:chemical synthesis / Q000494:pharmacology; D008954:Models, Biological; D015394:Molecular Structure; D010091:Oximes / Q000138:chemical synthesis / Q000494:pharmacology; D011960:Receptors, Estrogen / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D019809:Streptavidin / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D020798:Two-Hybrid System Techniques; D015003:Yeasts / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*
D010091:Oximes; D011960:Receptors, Estrogen; C120842:estrone oxime; D004970:Estrone; D019809:Streptavidin