Transition metal carbonyl oestrogen receptor assay

Abstract

Hormonal steroids, such as 17 β-estradiol derivatives, labelled with organometallic moieties have been synthesized and tested as markers for hormone receptor assay. Among the organometallic labels used were : Cr(CO)3 and Cr(CO)2(CS) whiclvcan be attached to the arene A ring of the steroid; CO2(CO)6 and Mo(η -C5H5)2(CO)4 which can be bonded to acetylenic groups introduced at the 17α-posǐtǐon of the five-membered steroidal ring. There is a spectral window at about 2000 cm-1 in the FT-IR spectra of the protein precipitated from lamb uterus cytosol which we reasoned could be used to detect the v(CO) modes of the metal carbonyl fragments of the organometallic labels. This indeed proved possible and the present detection level for 10,000-20,000 co-added scans at 4cm-l resolution is in the neighborhood of 100 fM. That specific rather than non-specific receptor sites were being detected was demonstrated by preparing an estradiol derivative doubly labelled with tritium and Cr(CO)3 and comparable receptor-site concentration levels were measured by both radiochemical analysis and FT-IR spectroscopy. The potential application of this new receptor assay technique in the early diagnosis of hormone-dependent cancers appears feasible. © 1985 IUPAC