DaSilva J N, van Lier J E
MRC Group in the Radiation Sciences, Faculty of Medicine, University of Sherbrooke, Quebec, Canada.
J Med Chem. 1990 Jan;33(1):430-4. doi: 10.1021/jm00163a066.
A series of 7 alpha-undecylestradiol derivatives, featuring various substituents at the end of the undecyl spacer chain, were synthesized and evaluated for their interaction with the estrogen receptor and nonreceptor sites. Their relative binding affinities (RBA) for calf uterine estrogen receptors were measured by competitive binding assays and varied between 0.5 and 8.4% of that of unlabeled 17 beta-estradiol. Enhanced lipophilicity and steric hindrance of the substituent on the end of the spacer chain resulted in decreased binding affinity for the estrogen receptor, while interactions with nonreceptor sites increased. RBA values were not affected by prolonged incubation times, suggesting a stable ligand-receptor complex. The potential to use the 7 alpha-undecylestradiol as a vector for site-selective delivery of diagnostic and therapeutic moieties to estrogen-receptor-positive human cancers is discussed.
合成了一系列7α-十一烷基雌二醇衍生物，这些衍生物在十一烷基间隔链末端具有各种取代基，并对它们与雌激素受体和非受体位点的相互作用进行了评估。通过竞争性结合试验测定了它们对小牛子宫雌激素受体的相对结合亲和力（RBA），其值在未标记的17β-雌二醇的0.5%至8.4%之间变化。间隔链末端取代基的亲脂性增强和空间位阻导致对雌激素受体的结合亲和力降低，而与非受体位点的相互作用增加。RBA值不受延长孵育时间的影响，表明配体-受体复合物稳定。讨论了使用7α-十一烷基雌二醇作为载体将诊断和治疗部分位点选择性递送至雌激素受体阳性人类癌症的潜力。
