120510-52-3Relevant academic research and scientific papers
AROMATIC COMPOUND, MODIFICATION CARRIER THAT USES SAME AND IS USED FOR SYNTHESIZING AN OLIGONUCLEOTIDE DERIVATIVE, OLIGONUCLEOTIDE DERIVATIVE, AND OLIGONUCLEOTIDE CONSTRUCT
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, (2012/11/06)
The present invention provides an oligonucleotide derivative that enables to easily synthesize an oligonucleotide derivative chemically modified at the 3'-end with two moieties each having a benzene or pyridine structure with a few steps, an aromatic compound serving as a precursor for preparing the modification carrier for synthesizing oligonucleotide derivative, and the oligonucleotide derivative and the oligonucleotide construct using the same, that is chemically modified at the 3'-end with two moieties each having a benzene or pyridine structure, and has good permeability through a cell membrane and excellent nuclease resistance. The modification carrier for synthesizing oligonucleotide derivative, comprising a unit and a carrier carrying the unit directly or via a linker, wherein the unit is represented by the formula (a): wherein, R1 to R6 each independently represent hydrogen or a substituent other than hydrogen; Z1 and Z2 each independently represent CH or nitrogen; and X represents oxygen or sulfur.
Synthesis of nuclease-resistant siRNAs possessing universal overhangs
Ueno, Yoshihito,Watanabe, Yuuji,Shibata, Aya,Yoshikawa, Kayo,Takano, Takashi,Kohara, Michinori,Kitade, Yukio
experimental part, p. 1974 - 1981 (2009/05/07)
RNA interference (RNAi) induced by small interfering RNA (siRNA) has emerged as a powerful technique for the silencing of gene expression at the post-transcriptional level. It has been shown that in the RNAi machinery, the 3′-overhang region of a guide strand (an antisense strand) of siRNA is recognized by the PAZ domain in the Argonaute protein, and the 2-nucleotide (nt) 3′-overhang is accommodated into a binding pocket composed of hydrophobic amino acids in the PAZ domain. Based on this background information, we designed and synthesized siRNAs possessing aromatic compounds at their 3′-overhang regions. It was found that the modified siRNAs possessing aromatic compounds are more potent than the siRNAs without the 3′-overhang regions. Further, the silencing activities of the modified siRNAs are almost equal to those of normal siRNAs with natural nucleosides at their 3′-overhang regions. We also found that the siRNAs possessing the aromatic compounds at their 3′-overhang region could be used to inhibit hepatitis C virus (HCV) replication. Moreover, the RNAs with aromatic groups at their 3′-ends were more resistant to nucleolytic degradation by snake venom phosphodiesterase (SVPD) (a 3′-exonuclease) than natural RNAs. The aromatic compounds described in this report do not have functional groups capable of forming hydrogen bonds with nucleobases. Therefore, we expect that they can serve as the universal overhang units that can improve the nuclease resistance of siRNAs.
Synthesis and properties of combinatorial libraries of phosphoramidates
Fathi, Reza,Rudolph, M. Jonathan,Gentles, Robert G.,Patel, Rina,MacMillan, Eric W.,Reitman, Michael S.,Pelham, David,Cook, Alan F.
, p. 5600 - 5609 (2007/10/03)
We have assembled a set of combinatorial libraries of phosphoramidates for pharmacological evaluation. A range of functionalized and unfunctionalized diols, representing a variety of diversity elements, were converted into their corresponding dimethoxytrityl H-phosphonate derivatives which were coupled to each other to produce H-phosphonate dimers and trimers. The H-phosphonate diesters were converted into phosphoramidates by reaction with a wide range of primary and secondary amines. Very large libraries (theoretically, in excess of one million compounds) possessing five sites of diversity were generated for use in our drug discovery program. Smaller libraries with lower molecular weights were also prepared in which only two monomeric units were coupled together and converted into their phosphoramidate derivatives. Methods for the attachment of both radioactive and nonradioactive labels, including 32phosphorus, tritium, and fluorescein, have been developed. Representative single sequences were also prepared and their chemical properties studied.
Towards Tumor Targeting with Copper-radiolabelled Macrocycle-Antibody Conjugates: Synthesis, Antibody Linkage, and Complexation Behaviour
Morphy, J. Richard,Parker, David,Kataky, Ritu,Eaton, Michael A. W.,Millican, Andrew T.,et al.
, p. 573 - 585 (2007/10/02)
A set of four tetra-azamacrocyclic ligands bearing aminomethylphenyl substituents have been prepared and may be attached to a monoclonal antibody via an intermediate thiol-specific vinylpyridine linker molecule.The resultant conjugates may be efficiently
