New Method Developed for Stereoselective Synthesis of Biologic Drug Substances

Researchers at Scripps Research and Bristol-Myers Squibb are touting phosphorus-sulfur incorporation as a scalable method for the production of antisense therapies.

Antisense drugs operate by binding to specific portions of genetic information - typically RNA. As such, their efficacy and safety are derived from their three-dimensional structures. Even slight variations, which often occur when these drug substances are produced using current synthetic methods, can be problematic.

Researchers at San Diego’s Scripps Research and Bristol-Myers Squibb recently developed a new method that allows for the highly controlled, stereoselective synthesis of oligonucleotides and similar compounds that can serve as active pharmaceutical ingredients.

Phosphorus-sulfur incorporation (PSI) uses P(V) compounds rather than the traditional P(III) compounds. According to Scripps researcher Phil Baran, replacing highly reactive P(III) with P(V) reagents allows for greater stereocontrol and a quicker route to the desired products. It also has the advantage of being useful at the discovery phase and scalable for commercial manufacturing.

To demonstrate its applicability, the researchers used PSI to synthesize antisense oligonucleotides similar to Spinraza (nusinersen), a treatment for spinal muscular atrophy, and cyclic dinucleotides (CDNs), a new class of cancer immunotherapy agents.

 

Emilie Branch

Emilie is responsible for strategic content development based on scientific areas of specialty for Nice Insight research articles and for assisting client content development across a range of industry channels. Prior to joining Nice Insight, Emilie worked at a strategy-based consulting firm focused on consumer ethnographic research. She also has experience as a contributing editor, and has worked as a freelance writer for a host of news and trends-related publications