Synthesis and biological properties of chimeric interferon-alpha 2b peptides

CLARA PEÑA; VIVIANA C. BLANK; VERÓNICA J. MARINO; LEONOR P. ROGUIN

PEPTIDES

Elsevier Inc.

Año: 2005 vol. 26 p. 1144 - 1149

0196-9781

We have previously reported the antiproliferative activity of synthetic sequences 29–35 and 122–139 of the interferon-alpha 2b (IFN-alpha 2b), 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, thedistance that separates residues 122 and 35 in the crystalline structure of the IFN-alpha 2b 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 125I-IFN-alpha 2b binding to WISH cell-membrane receptors was observed for both peptides. Results indicated that chimeric IFN-alpha 2b peptides behaved as partial agonists of the IFN-alpha 2b molecule and may be of interest for drug designpurposes.