Schlegel, Mark K.; Matsuda, Shigeo; Brown, Christopher R.; Harp, Joel M.; Barry, Joseph D.; Berman, Daniel; Castoreno, Adam; Schofield, Sally; Szeto, John; Manoharan, Muthiah; Charisse, Klaus; Egli, Martin; Maier, Martin A. published an article in 2021. The article was titled 《Overcoming GNA/RNA base-pairing limitations using isonucleotides improves the pharmacodynamic activity of ESC+ GalNAc-siRNAs》, and you may find the article in Nucleic Acids Research.Category: ethers-buliding-blocks The information in the text is summarized as follows:
We recently reported that RNAi-mediated off-target effects are important drivers of the hepatotoxicity observed for a subset of GalNAc-siRNA conjugates in rodents, and that these findings could be mitigated by seed-pairing destabilization using a single GNA nucleotide placed within the seed region of the guide strand. Here, we report further investigation of the unique and poorly understood GNA/RNA cross-pairing behavior to better inform GNA-containing siRNA design. A reexamination of published GNA homoduplex crystal structures, along with a novel structure containing a single (S)-GNA-A residue in duplex RNA, indicated that GNA nucleotides universally adopt a rotated nucleobase orientation within all duplex contexts. Such an orientation strongly affects GNA-C and GNA-G but not GNA-A or GNA-T pairing in GNA/RNA heteroduplexes. Transposition of the hydrogen-bond donor/acceptor pairs using the novel (S)-GNA-isocytidine and -isoguanosine nucleotides could rescue productive base-pairing with the complementary G or C ribonucleotides, resp. GalNAc-siRNAs containing these GNA isonucleotides showed an improved in vitro activity, a similar improvement in off-target profile, and maintained in vivo activity and guide strand liver levels more consistent with the parent siRNAs than those modified with isomeric GNA-C or -G, thereby expanding our toolbox for the design of siRNAs with minimized off-target activity. In addition to this study using N,N-Dimethylformamide Dimethyl Acetal, there are many other studies that have used N,N-Dimethylformamide Dimethyl Acetal(cas: 4637-24-5Category: ethers-buliding-blocks) was used in this study.
N,N-Dimethylformamide Dimethyl Acetal(cas: 4637-24-5) belongs to anime. Amines can be classified according to the nature and number of substituents on nitrogen. Aliphatic amines contain only H and alkyl substituents. Aromatic amines have the nitrogen atom connected to an aromatic ring.Important amines include amino acids, biogenic amines, trimethylamine, and aniline. Inorganic derivatives of ammonia are also called amines, such as monochloramine (NClH2).Category: ethers-buliding-blocks
Referemce:
Ether – Wikipedia,
Ether | (C2H5)2O – PubChem