Ligation Creates Permanent Thiol Links

A chemical ligation process has been devised for adding permanently organic functional groups and compounds to cysteine and other thiols (J. Am. Chem. Soc. 2006, 128, 2544). The selenium sulfide ligation and subsequent rearrangement with loss of the selenium was developed by David Crich and coworkers at the University of Illinois, Chicago.

Benjamin G. Davis of the University of Oxford, who helped develop a similar but impermanent disulfide-based chemical ligation method, comments that selenium sulfide ligations and rearrangements were known before but that Crich???s technique ???nicely combines them. As it stands, it will be a useful conjugation method for free thiols.??? If the reaction can be demonstrated to extend to protein-based thiols, as the paper suggests should be possible, the new reaction could be broadly useful for chemical protein ligation, Davis says.

Crich and coworkers note that ???applications in combinatorial chemistry and for the attachment of a wide variety of groups, including poly(ethylene glycol) and fluorous chains and oligosaccharide units to thiols of biological interest, are currently under development.???