Other approaches
Improving peptide synthesis also is an area of ongoing research. Researchers from Vanderbilt University recently reported
their efforts in overcoming a limitation in peptide synthesis, the incorporation of non-natural amino acids into the peptide
chain. The researchers noted that creation of amide bonds typically use methods that principally are based on dehydrative
approaches or oxidative and radical-based methods. Generally, carbon and nitrogen bear electrophilic and nucleophilic character,
respectively, during the carbon–nitrogen bond-forming step. In their work, the researchers showed the activation of amines
and nitroalkanes with an electrophilic iodine source to directly make amide products. The suggested mechanism showed that
the polarities of the two reactants were reversed during carbon–nitrogen bond formation relative to traditional approaches.
Looking forward, the researchers noted that using nitroalkanes as acyl anion equivalents provides a conceptually innovative
approach to amide and peptide synthesis, and one that may further engender more efficient peptide synthesis that relies on
enantioselective methods (7).
"Scientists from many disciplines have sought improved methods to streamline the synthesis of peptides through purely chemical
means in order to increase the diversity of the chemical tools available for the design of improved therapeutics," said Jeff
Johnston, professor of chemistry at Vanderbilt University, in a June 23, 2010, Vanderbilt University press release. "Our discovery
of a conceptually new approach to peptide synthesis brings this capability much closer to reality."
Patricia Van Arnum is a senior editor at Pharmaceutical Technology, 485 Route One South, Bldg F, First Floor, Iselin, NJ 08830 tel. 732.346.3072, pvanarnum@advanstar.com
.
References
1. T. Sawyer, Chem. Biol. Drug. Des.
73 (1), 3–6 (2009).
2. W. Wolfson, Chem. & Biol. 16 (9), 910–911 (2009).
3. J.B. Binder and R. Raines, Curr. Opin. Chem. Biol.
12 (6), 767–773 (2008).
4. H.E. Blackwell and R. Grubbs, Angew. Chem. Int. Ed. 37, 3281–3284 (1998).
5. G.H. Bird et al., Proc. Natl. Acad. Sci., DOI/10.1073pnas.1002713107 (June 18, 2010).
6. Q. Lin et al., Biorg. Med. Chem. Lett.
21 (5) 1472–1475 (2011).
7. B. Shen, D. Makely, and J.N. Johnston., Nature
465 (7301), 1027–1032 (2010).
|
