Enzymatic synthesis and bioactivity of estradiol derivative conjugates with different amino acids

A series of N-protected amino acid-estradiol derivative conjugates have been synthesized by coupling of 17β-aminoestra-1,3,5 (10)-trien-3-ol (1) or 17β-hydrazonoestra-1,3,5 (10)-trien-3-ol (2) with different amino acids via the catalysis of subtilisin Carlsberg in organic solvent. Various factors, including the structure of amino acid residue, different N-protecting groups of amino acids, different esters of carboxyl group and water content of the reaction media that influence the efficiency of enzymatic reactions were systematically studied. In vitro biological activity studies revealed that the binding interactions between estradiol derivative conjugates and estrogen receptor can be affected by the properties of the conjugated amino acid, but the effects of the change in binding properties did not result in changes in biological activities in both MCF-7 and HeLa cell lines.