Novel modified beta-interferons: gene cloning, expression, and biological activity in bacterial extracts.
A series of novel, modified interferons based on the structure of human beta-interferon have been expressed in Escherichia coli. Modified interferon genes were constructed from sequences derived from the natural beta-interferon gene, a synthetic beta-interferon gene, or a specific combination of the two. A total of 23 out of the 25 novel interferons exhibited antiviral (AV) and antiproliferative (AP) activity which varied from 3 to 230% and 8 to 490% of the values for beta-interferon, respectively. None of the novel interferons had only AV or AP activity, although one had a much reduced ratio of AV/AP activity compared with beta-interferon. Substitution of beta-interferon amino acids 2-7 or 28-46 resulted in interferons with significantly increased AP activity on Daudi lymphoblastoid cells (four- to fivefold). All the novel interferons except two with modifications in the 82-105 region reacted with a neutralizing beta-interferon monoclonal antibody.
D000595:Amino Acid Sequence; D001483:Base Sequence; D002455:Cell Division / Q000187:drug effects; D003001:Cloning, Molecular; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D005813:Genes, Synthetic; D006801:Humans; D007370:Interferon Type I / Q000096:biosynthesis / Q000235:genetics* / Q000494:pharmacology; D009500:Neutralization Tests; D009841:Oligonucleotides / Q000138:chemical synthesis; D011487:Protein Conformation; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014779:Virus Replication / Q000187:drug effects
D007370:Interferon Type I; D009841:Oligonucleotides; D011994:Recombinant Proteins