Photochemical preparation of peptide/glycopeptide-alpha-thioesters

CARB 86

Tyrone J Hogenauer, inmybubble@hotmail.com and Katja Michael, kmichael@utep.edu. Department of Chemistry, University of Texas at El Paso, 500 W. University Ave., El Paso, TX 79902
The recent development of the Native Chemical Ligation technique allows for the total synthesis of moderately sized proteins. While the NCL steps are usually high yielding, overall protein yields often suffer from low peptide-alpha-thioester yields. These preparations have opened doors for the generation of large peptides and glycopeptides, however, their use is often limited by unacceptable levels of epimerization, hydrolysis of the activated carboxylic acid or thioester under basic conditions, post-chain assembly manipulations prior to thioesterification, or incompatibility with the Fmoc/t-Bu protection chemistry. Therefore, there is a great demand for a universal and efficient method for the synthesis of peptide- and glycopeptide-alpha-thioesters. We describe the development of a novel resin with a photolabile nitroindoline linker, that allows for the synthesis of peptides or glycopeptides using standard Fmoc/t-Bu SPPS. Upon illumination with UV-light in the presence of a mercaptan and HOBt the (glycol)peptide-alpha-thioesters are generated by direct photorelease with minimal epimerization.
 

General Posters
6:00 PM-8:00 PM, Tuesday, August 21, 2007 BCEC -- Exhibit Hall - B2, Poster

Sci-Mix
8:00 PM-10:00 PM, Monday, August 20, 2007 BCEC -- Exhibit Hall - B2, Sci-Mix

Division of Carbohydrate Chemistry

The 234th ACS National Meeting, Boston, MA, August 19-23, 2007