Synthesis of functional proteins by mixing peptide motifs.
Here, we describe a synthetic approach for generating artificial proteins by the assemblage of naturally occurring peptide motifs. Two motifs respectively related to apoptosis induction and protein transduction were encrypted into different reading frames of an artificial gene (microgene), which was then polymerized; random frame shifts at the junctions between the microgene units yielded combinatorial polymers of three reading frames. Among the proteins created, #284 was found to penetrate through cell membranes and exert a strong apoptotic effect on several cancer cell lines. Because a simple linkage of these motifs was not sufficient to construct a bifunctional peptide, and the successful reconstitution was dependent on how they were joined together, the combinatorial strategy is important for reconstituting functions from mixtures of motifs. This microgene-based approach represents a novel system for creating proteins with desired functions.
Saito
Hirohide
H
Department of Protein Engineering, Japanese Foundation for Cancer Research, Toshima, Tokyo 170-8455, Japan.
Honma
Takako
T
Minamisawa
Tamiko
T
Yamazaki
Kanami
K
Noda
Tetsuo
T
Yamori
Takao
T
Shiba
Kiyotaka
K
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D015195:Drug Design; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D011108:Polymers / Q000494:pharmacology; D011506:Proteins / Q000138:chemical synthesis* / Q000494:pharmacology*
D011108:Polymers; D011506:Proteins; C528189:artificial protein 284