Development of interferon-gamma antagonists as an example of biotechnology application to approach new immunomodulators.
Recent applications of recombinant DNA technology have made possible the isolation and structural characterization of previously poorly-described proteins (e.g. Interferon-gamma (IFN gamma) and its specific receptors). These "recombinant proteins" can be developed as new therapeutics, or used in high specific screening. Structural information obtained from the studies on the recombinant proteins and their receptors, can then be used in computer assisted molecular modeling to design non-proteinaceous immunomodulatory, antiinflammatory and antineoplastic molecules. These novel compounds, able to modulate the functions of the endogenous IFN gamma, will show several advantages in respect to the recombinant proteins used as drugs. We would like to illustrate how the application of the modern biotechnology leads to the development of new drugs and, as an example, to describe the procedure which is followed in the case of the IFN gamma.
Garotta
G
G
Central Research Units, F. Hoffmann-La Roche, Basel, Switzerland.
Ozmen
L
L
Fountoulakis
M
M
D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D000595:Amino Acid Sequence; D000818:Animals; D001685:Biological Factors / Q000502:physiology; D016207:Cytokines; D006801:Humans; D007371:Interferon-gamma / Q000037:antagonists & inhibitors* / Q000502:physiology; D008954:Models, Biological; D008969:Molecular Sequence Data; D011971:Receptors, Immunologic / Q000502:physiology; D017471:Receptors, Interferon; D011994:Recombinant Proteins / Q000138:chemical synthesis / Q000494:pharmacology / Q000627:therapeutic use
D000276:Adjuvants, Immunologic; D001685:Biological Factors; D016207:Cytokines; D011971:Receptors, Immunologic; D017471:Receptors, Interferon; D011994:Recombinant Proteins; D007371:Interferon-gamma