0
Facebook
Volume 91 Issue 17 | p. 28 | Concentrates
Issue Date: April 29, 2013

Cross-Linking Technique Could Complement Peptide Stapling

Method stabilizes proteins without the need for metal catalysts or nonnatural amino acids
Department: Science & Technology
News Channels: Organic SCENE, Biological SCENE, JACS In C&EN
Keywords: Stapled peptides, chemical biology, hexafluorobenzene, bioconjugation, helix, breast cancer
[+]Enlarge
A new stapling technique uses hexafluorobenzene to link two segments of this peptide.
Credit: Adapted from J. Am. Chem. Soc.
A ribbon structure reaction scheme. On the left, one helix has two sulfide groups hanging off. On the right, the sulfide groups have both bound to the same fluorinated benzene ring.
 
A new stapling technique uses hexafluorobenzene to link two segments of this peptide.
Credit: Adapted from J. Am. Chem. Soc.

When chemists say they’re stapling a peptide, what they’re actually doing is cross-linking some of the amino acid side chains to make the peptide more stable or to adjust its properties. MIT’s Bradley L. Pentelute, Tufts University’s Yu-Shan Lin, and coworkers have developed a new stapling technique that could complement established methods (J. Am. Chem. Soc., DOI: 10.1021/ja400119t). The researchers originally planned to develop a mild way to arylate a cysteine thiol, and they were adapting a known reaction between thiols and hexafluorobenzene for that purpose. But two cysteines consistently added to the benzene species instead of one, so they decided to focus on cross-linking instead. Stapling traditionally calls for nonnatural amino acids and a metal catalyst, but the new technique doesn’t require them. It is compatible with protein synthesis techniques, as the team demonstrated by building a stabilized three-helix protein that binds to a breast cancer biomarker.

 
Chemical & Engineering News
ISSN 0009-2347
Copyright © American Chemical Society