ChemGenes Corporation

Wilmington, MA, United States

ChemGenes Corporation

Wilmington, MA, United States

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This invention is related to nucleic acid chemistry and describes novel 1,2-dithiolane functionalized nucleoside phosphoramidites (1, Chart 1) and corresponding solid supports (2, Chart 1). In addition to these derivatives, 1,2-dithiolane moiety can also be functionalized to at the various positions of the nucleobase and sugar part as shown in Schemes 1 to 8. The nucleosides of our invention carry a primary hydroxyl for DMTr (4,4-dimethoxytrityl) function for chain elongation. Furthermore, the phosphoramidite function is attached at the 3-hydroxyl of the nucleoside. This allows oligonucleotide chain extension under standard DNA and RNA synthesis chemistry conditions and techniques, thus leading to high quality oligonucleotides. These derivatives are useful for introduction of reactive thiol groups either at 3- or 5-end of the oligonucleotides on the solid supports such as gold, silver and quantum dots.


Srivastava S.C.,ChemGenes Corporation
Current protocols in nucleic acid chemistry / edited by Serge L. Beaucage ... [et al.] | Year: 2011

We have synthesized and studied the coupling properties of 3'-DMT-5'-CE phosphoramidites. The coupling efficiency per step surpasses 99% in the reverse-direction synthesis methodology, leading to high-purity RNA in a large number of 20- to 21-mers and long-chain oligonucleotides. Our data show that 5'→3' direction synthesis has a distinct advantage compared to the conventional method. As a result, this method of RNA synthesis is expected to be a very useful and practical method of choice for therapeutic-grade RNA. The phosphoramidites, Rev-A-n-bz, Rev-C-n-bz, Rev-C-n-ac, Rev-G-n-ac, and Rev-rU are routinely produced with an HPLC purity of greater than 98% and (31)P NMR purity greater than 99.5%. © 2011 by John Wiley & Sons, Inc.


The thiol modified oligonucleotides have vast number of applications in the field of nucleic acid chemistry. The conjugates generated by mono thiol groups are unstable at higher temperature, in high salt concentration buffers and in presence other thiols. There is strong need to develop a novel thiol modifier probes that can generate multiple thiol groups. Described herein are efficient processes and compounds, dithiolane phosphoramidites derivative and dithiolane succinyl supports. The advantage of our cyclic disulfide thiol modifier is multifold a) each incorporation introduces two thiol groups; b) it can be introduced at any desired site of oligonucleotides; c) The symmetrical branching nature of the spacer in the linker arm of dithiolane allows for clean oligo synthesis, where cleavage of the linker arm and thereby of loss of oligo chain is prevented. We have successfully made 20-mer oligonucleotide containing single dithiolane derivative at 3, and 21-mer oligonucleotides containing single dithiolane derivative at 5 or in the middle of the mixed base sequence. HPLC and ESI MS analysis of these oligonucleotides indicated satisfactory purity and correct composition of these oligos, respectively.


The present invention relates to novel phosphoramidites, A-n-bz, C-n-bz, C-n-ac, G-n-ac and U are produced with an HPLC purity of greater than 98% and ^(31)P NMR purity greater than 99%. A novel process of reverse 53 directed synthesis of RNA oligomers has been developed and disclosed. Using that method demonstrated high quality RNA synthesis with coupling efficiency approaching 99%.


The present invention is directed to n-alkylated synthetic nucleosides of high regiospecific purity and oligonucleotides that can be utilized for studies on reversal of cytotoxic and mutagenic DNA damage, and as diagnostic tools.


The present invention provides building blocks and methods for synthesizing very pure RNA in a form that can efficiently be modified at the 3 end. Reverse RNA monomer phosphoramidites have been developed for RNA synthesis in 53 direction, leading to very clean oligo synthesis that allows for the introduction of various modifications at the 3-end cleanly and efficiently. Higher coupling efficiency per step have been observed during automated oligo synthesis with the reverse RNA amidites disclosed herein, resulting in a greater ability to achieve higher purity and produce very long oligonucleotides. The use of the reverse RNA phosphoramidites in the synthetic process of this invention leads to oligonucleotides free of N+1 species.


Patent
Chemgenes Corporation | Date: 2011-12-21

The invention provides a novel group of azo quencher compositions that are useful as quenchers of fluorescence and to methods for making and using them. The quenchers contain an azo bond and 1,3,3-trimethyl-2-methyleneindoline ring system. The quenchers can be derivatized to facilitate their conjugation to a variety of biologically relevant compounds, including lipids, nucleic acids, peptides, proteins, and the like.


Patent
ChemGenes Corporation | Date: 2016-03-14

The present invention relates to novel process of reverse 53 directed synthesis of RNA oligomers in the range of about 100-mer to about 200-mer has been developed and disclosed. Using that method demonstrated high quality RNA synthesis with coupling efficiency approaching 99%.


The present invention relates to novel phosphoramidites, A-n-bz, C-n-bz, C-n-ac, G-n-ac and U are produced with an HPLC purity of greater than 98% and ^(31)P NMR purity greater than 99%. A novel process of reverse 53 directed synthesis of RNA oligomers has been developed and disclosed. Using that method demonstrated high quality RNA synthesis with coupling efficiency approaching 99%.


Trademark
ChemGenes Corporation | Date: 2010-03-02

Nucleic acid for laboratory and research use; nucleic acid sequences for other than medical and veterinary purposes; kits comprising chemical, biochemical and biotechnological products, namely, nucleic acids and enzymes; nucleic acid amplification reagents for research purposes; nucleic acids for industrial use. Diagnostic preparations for medical and veterinary medical purposes comprising nucleic acids and enzymes; blood test kits comprising diagnostic reagents and nucleic acids for in vitro medical diagnostic use; nucleic acid sequences for medical and veterinary purposes. Scientific and technological consultancy services in the field of analysis of nucleic acids; research and development of nucleic acids.

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