A P(V) platform for oligonucleotide synthesis
Yazhong Huang, Kyle W. Knouse, Shenjie Qiu, Wei Hao, Natalia M. Padial, Julien C. Vantourout, Bin Zheng, Stephen E. Mercer, Javier López-Ogalla, Rohan Narayan, Richard E. Olson, Donna G. Blackmond, Martin D. Eastgate, Michael A. Schmidt, Ivar M. McDonald, Phil S. Baran
Abstract
Platform for the synthesis of diverse oligos DNA is primarily viewed as a carrier of information encoded in the sequence of bases, but the chemistry of the phosphodiester backbone is crucial to oligonucleotide stability and structure. Building on previous work in synthetic P(V) phosphorothioate coupling chemistry, Huang et al . developed two new reagents for making phosphorodithioate- and phosphate-based linkages (see the Perspective by Virta). The authors incorporated all of these reagents into a unified P(V)-based synthesis platform capable of running at high efficiency on a commercial automated solid-phase synthesizer. They demonstrate the flexibility of this system by producing oligonucleotides with all three linkage types in specific positions. Access to such precisely constructed molecules opens new approaches to therapeutic oligonucleotide design. —MAF