55612-21-0Relevant articles and documents
Directed Evolution of 2′-Fluoro-Modified, RNA-Supported Carbohydrate Clusters That Bind Tightly to HIV Antibody 2G12
Redman, Richard L.,Krauss, Isaac J.
, p. 8565 - 8571 (2021)
Carbohydrate binding proteins (CBPs) are attractive targets in medicine and biology. Multivalency, with several glycans binding to several binding pockets in the CBP, is important for high-affinity interactions. Herein, we describe a novel platform for design of multivalent carbohydrate cluster ligands by directed evolution, in which serum-stable 2′-fluoro modified RNA (F-RNA) backbones evolve to present the glycan in optimal clusters. We have validated this method by the selection of oligomannose (Man9) glycan clusters from a sequence pool of ～1013 that bind to broadly neutralizing HIV antibody 2G12 with 13 to 36 nM affinities.
OLIGONUCLEOTIDE-LIGAND CONJUGATES AND PROCESS FOR THEIR PREPARATION
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Page/Page column 109, (2015/02/02)
The present invention relates to ligand conjugates of oligonucleotides (e.g., iRNA agents) and methods for their preparation. The ligands are derived primarily from monosaccharides These conjugates are useful for the in vivo delivery of oligonucleotides.
Synthesis and tumor uptake of 5-82Br- and 5-131I-labeled 5-halo-1-(2-fluoro-2-deoxy-β-D-ribofuranosyl)uracils
Mercer,Xu,Knaus,Wiebe
, p. 1289 - 1294 (2007/10/02)
A synthesis of 5-bromo- and 5-iodo-1-(2-fluoro-2-deoxy-β-D-ribofuranosyl)uracil (3 and 4) and their 5-82Br and 5-131I analogues has been developed. The tissue distribution of the radiolabeled compounds in BDF1 mice bearing Lewis lung tumors has been investigated. After injection of the radiolabeled analogues of compounds 3 and 4 there was a rapid initial excretion of activity. Compound 3 was excreted unchanged in the urine. Residual activity in mice after 4 h showed a distribution characteristic of bromide (Br-). Compound 4 was excreted mainly as unchanged starting material with increasing amounts of iodide (I-) detected at later time periods, in addition to 5-iodouridine and unidentified metabolites at shorter time periods. Both 3 and 4 demonstrated a remarkable in vivo stability relative to related 5-substituted nucleosides that do not contain the 2'-fluoro group. The tumor uptake was minimal, with only the 5-bromo analogue demonstrating a slight elevation in tumor to blood ratios relative to other tissues. Compounds 3 and 4 were shown to compete with thymidine for the same binding site in the transport of nucleosides across the cell membrane in mouse erythrocytes. The inhibition constants (K(i)) show that the compounds were weak competitors of thymidine binding to pyrimidine nucleoside transporter compared to physiological nucleosides. Other evidence indicates that compounds 3 and 4 are not substrates for mammalian kinase enzymes.
