Synthesis of functional proteins by mixing peptide motifs

Chemistry & Biology
Hirohide SaitoKiyotaka Shiba

Abstract

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.

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Citations

Oct 30, 2008·Proceedings of the National Academy of Sciences of the United States of America·Toru TsujiKiyotaka Shiba
Sep 21, 2007·Nucleic Acids Research·Hirohide SaitoKiyotaka Shiba
Aug 24, 2010·Current Opinion in Biotechnology·Kiyotaka Shiba
Nov 22, 2008·Biomaterials·Kenji KashiwagiKiyotaka Shiba
Dec 27, 2005·Current Opinion in Genetics & Development·Gilbert G Privé, Ari Melnick
Jul 22, 2015·Langmuir : the ACS Journal of Surfaces and Colloids·Norihisa NakayamaKen-ichi Sano
Feb 5, 2008·Biochemical and Biophysical Research Communications·Mark ItskoEitan Ben-Dov
Jan 21, 2010·Cell·Christina KielLuis Serrano
Oct 29, 2005·Chembiochem : a European Journal of Chemical Biology·Rainer FischerRoland Brock
Nov 3, 2009·Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan·Kiyotaka Shiba
Jul 2, 2009·Macromolecular Bioscience·Traian V ChirilaKiyotaka Shiba
Jan 18, 2006·Protein Engineering, Design & Selection : PEDS·Kenji KashiwagiKiyotaka Shiba
Jul 19, 2011·Chemical Communications : Chem Comm·Tatsuya MurakamiKiyotaka Shiba
Aug 2, 2007·Biomacromolecules·Kiyotaka Shiba, Tamiko Minamisawa
Oct 2, 2008·Biomacromolecules·Katsutoshi KokubunKiyotaka Shiba
Jan 21, 2010·Langmuir : the ACS Journal of Surfaces and Colloids·Ken-ichi SanoKiyotaka Shiba
Feb 25, 2015·Langmuir : the ACS Journal of Surfaces and Colloids·Norihisa NakayamaKen-Ichi Sano

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