Winner: 2022 Organic Division Horizon Prize: Robert Robinson Award in Synthetic Organic Chemistry
For the discovery of a sustainable and scalable platform of P(V) reagents for the synthesis of stereodefined and variable phosphate chimeric oligonucleotides, and their application to phosphorylation, bioconjugation, and chiral phosphine synthesis.
Celebrate Team P(V)
Based at Bristol-Myers Squibb and the Scripps Research Institute, the P(V) team won the prize for discovering a series of compounds capable of joining molecules together with different phosphorous linkages in a highly selective and programable fashion. These sustainable new reagents can be applied in a wide variety of settings, both in solution and in solid-phase, enabling the discovery of new therapeutics.Read more
Oligonucleotides are short DNA or RNA molecules that serve as the starting point for many synthetic biology applications. The team’s work envisaged a new platform to make oligonucleotides, confronting an established dogma in the field that phosphorus in the +5 oxidation state was not feasible in synthesis.
The team demonstrated that the +5 oxidation state was not only feasible, but offers significant advantages in reactivity, stability and sustainability, showing great promise in both clinical development and as disease modifying agents.
The teamSee full team
Phil Baran, Professor, Scripps
Donna Blackmond, Professor, Scripps
Justine DeGruyter, PhD student, Scripps
Martin Eastgate, Executive Director, BMS
Rick Ewing, Director, BMS
Chao Hang, Researcher, BMS
Wei Hao, Post-Doc, Scripps
Yazhong Huang, Researcher, BMS
James Kempson, Researcher, BMS
Cian Kingston, Post-Doc, Scripps
Kyle Knouse, PhD student, Scripps
Javier Lopez-Ogalla, Post-Doc, Scripps
Ivar McDonald, Researcher, BMS
Stephen Mercer, Researcher, BMS
Natalia Munoz Padial, Post-Doc, Scripps
Rohan Narayan, Post-Doc, Scripps
Rick Olson, Researcher, BMS
Peter Park, Researcher, BMS
Shenjie Qiu, Researcher, BMS
Antonio Ramirez, Researcher, BMS
Nazaret Rivas-Bascon, Post-Doc, Scripps
Michael Schmidt, Researcher, BMS
Julien Vantourout, Post-Doc, Scripps
Qinggang Wang, Researcher, BMS
Matthew Winston, Researcher, BMS
Dongmin Xu, Post-Doc, Scripps
Changxia Yuan, Researcher , BMS
Bin Zheng, Researcher, BMS
Jason Zhu, Researcher, BMS
Ye Zhu, Researcher, BMS
Why is this work so important and exciting?
Michael Schmidt: This work is exciting as it allows rapid access to a new chemical space in a wide number of modalities containing phosphorous, from chiral ligands, to bioconjugate probes and new frontiers in ASO research, to name a few.
What different strengths did different people bring to the team?
Bin Zheng: This project spans multiple fields from small molecules to ASOs. Requiring people with expertise in different areas, such as innovative concepts, analytical methods, drug discovery, solid phase synthesis and scaleup for material supply. Each member of the team brought necessary skills to the success of the project.
How will this work be used in real life applications?
Yazhong Huang: Because chiral PS oligos and oligos with other linkages can be easily synthesized through P(V) chemistry, they will certainly trigger more extensive studies of their physicochemical and pharmacologic properties, and their impacts on clinical efficacy and safety profiles.
How do you see this work developing over the next few years, and what is next for this research?
Martin Eastgate: Hopefully, researchers outside of our team will find use in these reagents and explore the implications of chimeric oligonucleotides as therapeutic agents – gathering data around the implications of site-specific modifications enabled through this technology. The next step in oligonucleotide synthesis is to explore new solid-phase supports that can continue to deliver improved yields and higher loadings to improve the sustainability of oligonucleotide manufacturing. We hope researchers will find these reagents useful and push the science in new directions!
What inspires or motivates your team?
Jason Zhu: Taking risks and aiming high to impact chemical research in a fundamental way.
What is the importance of collaboration in the chemical sciences?
Professor Phil Baran: Truly great things are possible when a team of talented scientists bringing unique skills to the table are all focused on a common mission. Without this collaboration I doubt this chemistry would have come to be.
Michael Schmidt: The importance of collaboration cannot be understated. The union of many different groups with many different points of view provides multiple angles of attack at a problem. Our work, was a discovery chemistry challenge, with a process chemistry inspired concept and many academic solutions, extensions and applications. This work would not have been possible in a silo.
Martin Eastgate: Collaboration is critical in any field, but especially in STEM. Taking on big scientific challenges requires multiple perspectives, insight gain from diverse experiences and a team spirit to overcome the numerous obstacles faced in research. One of the main drivers of success of our team was bringing together medicinal chemists, process chemists and academic researchers to take on a big challenge in a new way. The different views and perspectives from each member of the team helped us identify issues, solve problems quickly and seek novel applications where this work could have impact. This work could not have existed without this team’s exceptional collaborative spirit.
What advice would you give to a young person considering a career in chemistry?
Martin Eastgate: Have fun, follow your passion, collaborate and approach problems with an open mind!