Novel Approach Could Lead to Creation of New Thiophosphate-Based Nucleotide Drugs

Scientists at Scripps Research and Bristol-Myers Squibb have created a novel tool for precisely controlling the stereochemistry of thiophosphates, found in some promising new drugs that target genetic molecules and other disease targets.

Called phosphorus-sulfur incorporation (PSI ), the technology acts like an atomic glue gun, binding nucleosides into oligomers with specific, preprogrammed spatial configurations at the thiophosphate linkage, according to the team. These linkages are analogues of nature's method of connecting nucleosides and offer multiple advantages to drug development, but add the complexity of stereochemistry at the phosphorous atom, note the researchers, who add that PSI provides an inexpensive and simple method to enable the development of single isomers of these compounds, which can have hundreds of thousands of stereoisomers.

The study (“ Unlocking P(V): Reagents for chiral phosphorothioate synthesis ”) appears in Science .

“Phosphorothioate nucleotides have emerged as ...