Vessieres A, Jaouen G, Gruselle M, Rossignol J L, Savignac M, Top S, Greenfield S
Ecole Nationale Supérieure de Chimie de Paris, U.A. C.N.R.S., France.
J Steroid Biochem. 1988;30(1-6):301-6. doi: 10.1016/0022-4731(88)90111-2.
Twelve novel organometallic derivatives of estradiol were synthesized with the aim of utilizing organometallic cold bioprobes as radioisotopic labels substitutes for steroid hormone receptor assays. For this purpose, we envisaged the attachment of several stable cobalt, molybdenum, osmium carbonyl clusters (tetra- and pentanuclear species) at estradiol 17 alpha-, 16 alpha-, 2- or 4-positions. The binding affinity of these new complexes for uterine estradiol receptor has been measured by the competitive binding method. The results show that the 17 alpha-position can tolerate substitution by bulky organometallic groups (especially in the case of cobalt and molybdenum carbonyl clusters). Estradiol derivatives which are functionalized at C-4 and C-16 alpha bind estradiol receptor with reasonable affinity and the RBA values are the same for the complexed and uncomplexed hormones. The 2- position is more sensitive to organometallic substitution and the complexation at the 2- alkyne results in a dramatic decrease of the RBA values. These results show that the attachment of polynuclear moieties in estradiol 17 alpha-, 4- and 16 alpha-, positions gives rise to compounds which are of potential utility in a new non-radioisotopic receptor assay since the metal-carbonyl markers are readily detected by high-sensitivity Fourier-transform infra-red spectroscopy.
合成了12种新型的雌二醇有机金属衍生物，目的是利用有机金属冷生物探针作为类固醇激素受体测定中放射性同位素标记的替代品。为此，我们设想在雌二醇的17α-、16α-、2-或4-位连接几种稳定的钴、钼、锇羰基簇（四核和五核物种）。通过竞争结合法测定了这些新配合物对子宫雌二醇受体的结合亲和力。结果表明，17α-位能够耐受庞大有机金属基团的取代（特别是在钴和钼羰基簇的情况下）。在C-4和C-16α位官能化的雌二醇衍生物以合理的亲和力结合雌二醇受体，并且络合和未络合激素的相对结合活性（RBA）值相同。2-位对有机金属取代更敏感，2-炔烃处的络合导致RBA值急剧下降。这些结果表明，在雌二醇的17α-、4-和16α-位连接多核部分会产生在新型非放射性同位素受体测定中具有潜在用途的化合物，因为金属羰基标记物很容易通过高灵敏度傅里叶变换红外光谱检测到。
