The de novo protein albebetin has been engineered (J. Mol. Biol. 1992, 225, 927-931) to form a predesigned tertiary fold that has not yet been observed in natural proteins. Analysis of albebetin expressed in a cell-free system and in Escherichia coli revealed its compactness, relative stability, and the secondary structure close to the predesigned one. The blast-transforming biological activity of human interferon was grafted to albebetin by attachment of an eight amino acid interferon fragment to the N-terminus of albebetin next to its first methionine residue. The chimeric protein was expressed in a wheat germ cell-free translation system and tested for its structural properties, receptor binding, and biological activity. According to the tests, albebetin incorporating the active interferon fragment has a compact and relatively stable structure, and binds the murine thymocyte receptor effectively. It activates the blast transformation reaction of thymocyte cells even more efficiently than human interferon at low concentrations.