Interaction Study of Different Forms of Human Recombinant Anti-Mullerian Hormone with a Chimeric Analogue of the AMH Type II Receptor

Abstract—

Anti-mullerian hormone (AMH), a homodimeric glycoprotein, described over 70 years ago by A. Jost, is the least studied member of the transforming growth factor beta superfamily. Despite the antitumor activity of AMH discovered at the end of the last century, creation of effective AMH-based drugs is hampered primarily by the lack of information on the mechanism of interaction of various AMH forms with a specific type II receptor (MISRII). Previously, we have shown that not only the full-length activated hormone but also its C-terminal fragment (C-rAMH) could bind to MISRII. In this work, using the surface plasmon resonance technique, we have compared the interaction of three forms of recombinant AMH (rAMH) with the MISRII analogue—the chimeric protein MISRII-Fc containing AMH type II receptor and-Fc fragment of the human IgG1 heavy chain. Comparison of the binding of MISRII-Fc, immobilized on a chip with group specificity for human immunoglobulins, to C-rAMH, to intact rAMH (pro-rAMH), and to rAMH containing one uncleaved monomer (hc-rAMH), showed that the K_D of the complexes increased: 1.7 nM, 88 nM and 110 nM, respectively. Thus, we have shown that the C-terminal fragment of AMH exhibits the maximum affinity for the recombinant MISRII analogue, thus indicating the prospects for the development of drugs based on this hormone derivative.