REVIEW OF RECENT DEVELOPMENTS IN THE MOLECULAR CHARACTERIZATION OF RECOMBINANT ALPHA-INTERFERONS ON THE 40TH ANNIVERSARY OF THE DISCOVERY OF INTERFERON

Recombinant alfa interferons (IFN-alpha s) are approved worldwide for the treatment of a variety of cancers and diseases of virologic origin . A series of recent advances in the molecular characterization of rec ombinant IFN-alpha s have allowed the determination of the three-dimen sional IFN-alpha(2b) structure by high-resolution x-ray crystallograph y. We review here recent developments in our understanding of the mole cular and physicochemical properties of recombinant IFN-alpha, includi ng our current state of knowledge of the IFN-alpha gene family and the multiple species of human leukocyte IFN. Based on the reported three- dimensional structure of IFN-alpha(2b), we propose a molecular model f or the IFN-alpha(2b) receptor complex and predict models for the natur ally occurring subtypes IFN-alpha(1) and IFN-alpha(8), as well as the synthetic, non-naturally occurring consensus IFN. Such models provide molecular insights into the mechanism of action of IFN-alpha.