Programmable site-selective labeling of oligonucleotides based on carbene catalysis

Abstract

Site-selective modification of oligonucleotides serves as an indispensable tool in many fields of research including research of fundamental biological processes, biotechnology, and nanotechnology. Here we report chemo- and regioselective modification of oligonucleotides based on rhodium(I)-carbene catalysis in a programmable fashion. Extensive screening identifies a rhodium(I)-catalyst that displays robust chemoselectivity toward base-unpaired guanosines in single and double-strand oligonucleotides with structurally complex secondary structures. Moreover, high regioselectivity among multiple guanosines in a substrate is achieved by introducing guanosine-bulge loops in a duplex. This approach allows the introduction of multiple unique functional handles in an iterative fashion, the utility of which is exemplified in DNA-protein cross-linking in cell lysates.

Stereoselective RNA reaction with chiral 2′-OH acylating agents

“…In addition, given the rapid development of RNAs as therapeutic agents, establishing methods to locally substitute RNA for conjugation is also of substantial interest; 5,45,48 however, it is signicantly challenging, due to the large number of chemically similar groups in the biopolymer. In this light, our observation of the highly selective stoichiometric labeling reaction of (R)azidoethyl-2 seems promising (Fig.…”

Organometallic catalysis in aqueous and biological environments: harnessing the power of metal carbenes

“…8c ). 96 The utility of this approach was further showcased by performing DNA-protein cross-linking in cell lysate.…”

Substrate Selectivity Imparted by Self‐Assembled Molecular Containers and Catalysts

“…His current research interest is in the design of extended aromatic compounds with self-assembling properties for supramolecular catalysis and recognition in organic as well as aqueous media. site selectivity in the acetonylation of base-unpaired guanosines in oligonucleotides [7] was recently reported mediated by rhodium(I)-carbene catalysis.…”