91592-85-7Relevant articles and documents
CYCLIC DINUCLEOTIDES AS ANTICANCER AGENTS
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Paragraph 1568; 1571; 1572, (2019/02/13)
The present invention is directed to compounds of the formulae I, II and III as shown below wherein all substituents are defined herein, as well as pharmaceutically acceptable compositions comprising compounds of the invention and methods of using said compositions in the treatment of various disorders.
Nucleobase and ribose modifications control immunostimulation by a MicroRNA-122-mimetic RNA
Peacock, Hayden,Fucini, Raymond V.,Jayalath, Prasanna,Ibarra-Soza, Jose M.,Haringsma, Henry J.,Flanagan, W. Michael,Willingham, Aarron,Beal, Peter A.
, p. 9200 - 9203 (2011/08/04)
Immune stimulation is a significant hurdle in the development of effective and safe RNA interference therapeutics. Here, we address this problem in the context of a mimic of microRNA-122 by employing novel nucleobase and known 2′-ribose modifications. The
A chemical method for site-specific modification of RNA: The convertible nucleoside approach
Allerson, Charles R.,Chen, Swaine L.,Verdine, Gregory L.
, p. 7423 - 7433 (2007/10/03)
Knowledge of RNA structure can greatly facilitate the understanding of its biological function. However, the physical properties of RNA, especially its conformational heterogeneity, present an impediment to high-resolution structural analysis. Thus,lower resolution methods such as biochemical probing, phylogenetic analysis, and molecular modeling have come to serve an important role in RNA science. This situation has created the need for a means by which to constrain RNA structure, either to reduce its conformational flexibility or to help distinguish between alternative structural models. To address this need, we have developed chemistry that permits the site-specific introduction of functionalizable tethers into RNA. Here we report the design and synthesis of reagents for use in solid-phase RNA synthesis that allow the functionalization of the base moiety of C, C, and A residues. Upon incorporation into oligonucleotides and subsequent treatment with alkylamines, the convertible nucleoside derivatives reported here give rise to functionally tethered N4-alkyl-C, N6-alkyl-A, and N2-alkyl-G residues in RNA. The derivatized RNAs can then be used to target the attachment of chemical probes or the placement of disulfide cross-links as structural constraints. The attachment of nonnatural functional groups to RNA in this fashion provides a powerful means of both probing its structural environment and constraining its conformation. The size and functionality of the N-alkyl modification is determined solely by the choice of alkylamine, thereby permitting the preparation of a wide range of functionally tethered RNAs.
