Chemical Synthesis of Reagents for Peptide Coupling
Inventors: Ronald Raines, Laura Kiessling, Bradley Nilsson, Matthew Soellner, Yi He, Ronald Hinklin
The Wisconsin Alumni Research Foundation (WARF) is seeking commercial partners interested in developing improved methods for synthesizing phosphinothiol reagents.
The Staudinger ligation method for synthesizing peptides requires phosphinothiol reagents that are not commercially available. The current method for making phosphinothiols is complicated (involving four steps) and time-consuming, uses dangerous chemicals, may result in tar-like products, is difficult to effect on a large scale and produces an overall yield of only 39 percent.
UW-Madison researchers have developed improved methods for synthesizing phosphinothiol reagents. These synthesis techniques take advantage of phosphorus’s strong interaction with boron, and are based on an easily prepared alkylating agent and a commercially available borane-organophosphine complex. In the methods, the alkylating agent is reacted with the borane-organophosphine complex. Disrupting the resulting phosphine-borane complex and removing the protecting group generates the phosphinothiol reagents.
- Phosphinothiol production
- Requires one less step than the current method
- Provides an overall yield of 74 percent
- Can be used to create a limitless variety of phosphinothiols
- Intermediary phosphine-borane complex is stable to air and moisture, allowing storage at room temperature for several months.