Ontorii Inc

Boston, MA, United States

Ontorii Inc

Boston, MA, United States
Time filter
Source Type

Zlatev I.,Alnylam Pharmaceuticals | Zlatev I.,Ontorii Inc | Manoharan M.,Alnylam Pharmaceuticals | Vasseur J.-J.,Montpellier University | Morvan F.,Montpellier University
Current Protocols in Nucleic Acid Chemistry | Year: 2012

A chemical method for the solid-phase synthesis of 5'-triphosphate oligonucleotides is described. The full-length oligonucleotides are first constructed using standard solidphase DNA/RNA synthesis, and then efficient implementation of a sequential 4-steps synthetic procedure, executed either manually or in a fully automated fashion, affords the corresponding solid-supported 5'-triphosphate oligonucleotides. Using this synthetic procedure, the full-length 5'-hydroxyl oligonucleotides are initially transformed into the corresponding 5'-H-phosphonate mono esters, subsequently oxidized in the presence of imidazole to the activated 5'-phosphorimidazolidates, and finally reacted with pyrophosphate on the solid support. The method uses safe, stable, and inexpensive reagents, and the process is scalable and readily applicable to automated synthesis compatible with the current commercially available DNA/RNA synthesizers. After cleavage from the solid support and deprotection, a range ofDNA, RNA, and chemically modified 5'-triphosphate oligonucleotides are obtained in a convenient and efficient manner and isolated in good yields after HPLC purification. Curr. Protoc. Nucleic Acid Chem. 50:1.28.1-1.28.16. © 2012 by John Wiley & Sons, Inc.

Zlatev I.,Alnylam Pharmaceuticals | Zlatev I.,Ontorii Inc. | Lackey J.G.,Alnylam Pharmaceuticals | Lackey J.G.,Agilent Technologies | And 8 more authors.
Bioorganic and Medicinal Chemistry | Year: 2013

A fully automated chemical method for the parallel and high-throughput solid-phase synthesis of 5′-triphosphate and 5′-diphosphate oligonucleotides is described. The desired full-length oligonucleotides were first constructed using standard automated DNA/RNA solid-phase synthesis procedures. Then, on the same column and instrument, efficient implementation of an uninterrupted sequential cycle afforded the corresponding unmodified or chemically modified 5′-triphosphates and 5′-diphosphates. The method was readily translated into a scalable and high-throughput synthesis protocol compatible with the current DNA/RNA synthesizers yielding a large variety of unique 5′-polyphosphorylated oligonucleotides. Using this approach, we accomplished the synthesis of chemically modified 5′-triphosphate oligonucleotides that were annealed to form small-interfering RNAs (ppp-siRNAs), a potentially interesting class of novel RNAi therapeutic tools. The attachment of the 5′-triphosphate group to the passenger strand of a siRNA construct did not induce a significant improvement in the in vitro RNAi-mediated gene silencing activity nor a strong specific in vitro RIG-I activation. The reported method will enable the screening of many chemically modified ppp-siRNAs, resulting in a novel bi-functional RNAi therapeutic platform. © 2012 Elsevier Ltd. All rights reserved.

Cassar D.J.,University of East Anglia | Nagaradja E.,University of East Anglia | Nagaradja E.,CNRS Laboratory of Molecular and Thio-Organic Chemistry | Butler D.C.D.,Queen Mary, University of London | And 3 more authors.
Organic Letters | Year: 2012

The Friedel - Crafts reaction of (η 4- tetraphenylcyclobutadiene)(η 5-carbomethoxycyclopentadienyl) cobalt with acid chlorides/aluminum chloride resulted exclusively in para-phenyl acylation. Both monoacylated (1.1 equiv of RCOCl/AlCl 3) and tetraacylated products (>4 equiv of RCOCl/AlCl 3) were synthesized. Reaction of PhCC(o-RC 6H 4) (R = Me, i-Pr) with Na(C 5H 4CO 2Me) and CoCl(PPh 3) 3 gave predominantly (η 4-1,3-diaryl-2,4-diphenylcyclobutadiene) (η 5-carbomethoxycyclopentadienyl)cobalt metallocenes (1,3-[trans] vs 1,2-[cis] selectivity up to 6:1). Conformational control of Friedel - Crafts reactions on the major isomers gave exclusively para-acylation of the unsubstituted phenyl groups. © 2012 American Chemical Society.

Ontorii Inc | Date: 2010-07-06

Described herein are nucleic acid prodrugs and nucleic acid prodrugs comprising chiral phosphorous moieties. Also described herein are methods of making and using nucleic acid prodrugs and nucleic acid prodrugs comprising chiral phosphorous moieties.

Loading Ontorii Inc collaborators
Loading Ontorii Inc collaborators