Synthesis and biological properties of chimeric interferon-alpha2b peptides.
We have previously reported the antiproliferative activity of synthetic sequences 29-35 and 122-139 of the interferon-alpha2b (IFN-alpha2b), both probably representing a common receptor recognition domain. In the search of new peptidic agonists, we designed and synthesized the linear peptide (Gly)2-122-137-Gly138-Gly29-30-35-(Gly)2, in which Gly residues replaced the 138 and 29 Cys bound through a disulfide bridge in the native cytokine. Additionally, a cyclic analog was obtained by reaction of the N- and C-terminal ends of the linear fragment. Thus, the distance that separates residues 122 and 35 in the crystalline structure of the IFN-alpha2b was maintained through a (Gly)4 bridge. When the influence of chimeric peptides on the proliferation of WISH cells was studied, it was shown that both derivatives significantly diminished cell growth. A more evident inhibitory effect on (125)I-IFN-alpha2b binding to WISH cell-membrane receptors was observed for both peptides. Results indicated that chimeric IFN-alpha2b peptides behaved as partial agonists of the IFN-alpha2b molecule and may be of interest for drug design purposes.
Peña
Clara
C
Instituto de Química y Fisicoquímica Biológicas (UBA-CONICET), Facultad de Farmacia y Bioquímica, Junin 956, 1113 Buenos Aires, Argentina. clara@qb.ffyb.uba.ar
Blank
Viviana C
VC
Marino
Verónica J
VJ
Roguin
Leonor P
LP
D000595:Amino Acid Sequence; D001667:Binding, Competitive; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000494:pharmacology*; D010456:Peptides, Cyclic / Q000138:chemical synthesis / Q000494:pharmacology*; D011487:Protein Conformation; D017471:Receptors, Interferon / Q000819:agonists*; D011994:Recombinant Proteins
C504513:(Gly)2-interferon alpha2b(122-137)-Gly(138)-Gly(139)-interferon alpha2b(30-35)-(Gly)2; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D010446:Peptide Fragments; D010456:Peptides, Cyclic; D017471:Receptors, Interferon; D011994:Recombinant Proteins; C504514:cyclo((Gly)2-interferon alpha2b(122-137)-Gly(138)-Gly(139)-interferon alpha2b(30-35)-(Gly)2)