DNA-modularized construction of bivalent ligands precisely regulates receptor binding and activation

(Chem 9, 901–923; April 13, 2023) The original version of this article published on January 2 unfortunately contained a few errors in the graphical abstract and Figures 1 and 5. In Figure 1B, the position of the 5′-terminal protecting group and 3′-terminal protecting group of natural deoxynucleotides should have been exchanged to be more consistent with the commercial natural deoxynucleotides in DNA solid-phase synthesis. In Figure 1D, the pharmacophore module B should have been connected with the 5′-terminal of the adjacent natural deoxynucleotide, and the pharmacophore module X should have been connected with the 3′-terminal of the adjacent natural deoxynucleotide in the “processing” procedure of the DNA synthesizer. In Figure 5A, the pharmacophore module B should have been connected with the 5′-terminal of the adjacent adenine deoxynucleotide (“AA”), and the pharmacophore module X should have been connected with the 3′-terminal of the adjacent AA. In the graphical abstract, the scheme in the “processing” procedure of the DNA synthesizer should have been corrected in sync with Figure 1D. These errors were corrected online on January 28. Thereafter, the authors unfortunately noticed a few additional errors. In Figure 1D, the pharmacophore module B should have been connected with the 5′-terminal of the adjacent natural deoxynucleotide by the other hydroxyl group, and the pharmacophore module X should have been connected with the 3′-terminal of the adjacent natural deoxynucleotide by the ending hydroxyl group in the “processing” procedure of the DNA synthesizer. In Figure 5A, the pharmacophore module X should have been connected with the 3′-terminal of the adjacent AA by the ending hydroxyl group. And in the graphical abstract, the scheme in the “processing” procedure of the DNA synthesizer should have been corrected in sync with Figure 1D. The graphical abstract and Figures 1 and 5 have now been corrected online again, and both sets of revisions appear below. The authors regret these errors and any confusion the multiple revisions may have caused. DNA-modularized construction of bivalent ligands precisely regulates receptor binding and activationZhao et al.ChemJanuary 2, 2023In BriefWe develop a DNA-modularized strategy capable of constructing bivalent ligands in a precise, automatic, and high-throughput manner. By regulating the number and permutation of the DNA spacer, the two pharmacophores of bivalent ligands are adjusted with a defined distance and versatile orientation. We successfully constructed a bivalent molecule exhibiting a single-nucleotide difference in selective activation of M1 muscarinic acetylcholine receptors. This strategy can be extended to the construction of many bivalent ligands for biomedical applications. Full-Text PDF