Sidney M. Hecht
Arizona State University
Talk Title
Ribosomal Synthesis of Peptides and Proteins Containing Non-Canonical Amino Acids
Presentation Time
SESSION 11: PEPTIDE DESIGN AND FUNCTION
Wednesday, June 28, 2023, at 02:45 pm - 03:10 pm
Several strategies now exist for the ribosomal synthesis of peptides and proteins containing non-proteinogenic amino acids. These enable the incorporation of one or more modified amino acids into predetermined positions in a peptide or protein. While a wide variety of amino acid side chains not found in natural proteins can be incorporated, bacterial ribosomes do not incorporate amino acid analogues such as D-amino acids or β-amino acids to a reasonable extent.
In the past several years, we have developed a strategy for modifying the 23S ribosomal RNA in E. coli ribosomes; this is the ribosomal constituent that mediates the peptide bond formation. By the use of structurally modified puromycin analogues, libraries of clones harboring plasmids with modified 23S rRNAs can be screened to identify clones capable of incorporating modified amino acids not normally incorporated by bacterial ribosomes.
Presently, I will discuss the incorporation into peptides and proteins of D-amino acids, β-amino acids, dipeptides and dipeptidomimetics, as well as nucleobase amino acids. Unique properties of the derived proteins will be described, including their ability to alter bacterial phenotype, and modulate gene expression in mammalian cells.
Sidney M. Hecht is the director for the Center for BioEnergetics in the Biodesign Institute at Arizona State University. He researches diseases caused by defects in the body's energy production processes. Energy production is similar mechanistically to other molecular processes that he has studied extensively. He played a key role in the development of Hycamtin, a drug used to treat ovarian and lung cancer, as well as the study of the mechanism of the anti-tumor agent bleomycin.
In a career spanning more than three decades, Professor Hecht has held both academic and industrial research positions. He joins ASU from the University of Virginia, where he was a professor of both chemistry and biology. From 1981 to 1987, he concurrently held leadership positions in research and development for Smith Kline and French Laboratories. Prior to his 28 years at the University of Virginia, he was a faculty member at MIT. Hecht is the co-founder of Edison Pharmaceuticals, a pharmaceutical company focusing on inherited mitochondrial disorders. He earned a B.A. in chemistry from the University of Rochester and a Ph.D. in chemistry with emphasis in biochemistry from the University of Illinois.
