Metkinen Chemistry - reagents for DNA and RNA synthesis!

来自 : 发布时间：2024-05-10

Metkinen Chemistry focuses on research and manufacture of reagents for RNA and DNA synthesis. We have expert knowledge of nucleoside chemistry, reagents for oligonucleotide synthesis, phosphoramidites and various solid supports. Reagents for oligo synthesis product line include Truly Universal solid support, Chemical Phosphorylation Reagent and Trimer (codon) Phosphoramidites. Possible applications encompass combinatorial oligonucletide libraries with trimer (codon) phosphoramidites, oligo synthesis using our Truly Universal solid support and convenient purification of oligonucleotide 5\'-phosphates with Chemical Phosphorylation Reagent. Today the efforts of Metkinen Chemistry are concentrated on our extensive line of purine nucleosides. Ultra-pure purine nucleoside analogs are used in the development of oligonucleotide therapeutics and in research applications. The new products, namely 3\'- Amino-2\',3\'-dideoxy-A and G nucleosides serve as building blocks for oligonucleotides that are resistant to enzymatic degradation. Another set of new nucleosides - 2\'-deoxy-2\'-fluoro-A and G, as well as 2\'-deoxy-2\'-amino-A and G are popular building clocks for the stabilization of small interfering RNAs (siRNAs) and aptamers. Metkinen Chemistry\'s biotransformation technology addresses the problems of traditional synthetic methods and offers alternative variants of biotransformation. Our flexibility and expertise allow Metkinen Chemistry to cater to a range of customer needs: from one-off oligonucleotide synthesis in academia to large-scale commercial production. Naturally this is reflected in appropriate discounts applied according to order size.Synthetic RNA oligonucleotides, incorporating 2\'-Deoxy-2\'-fluoro-nucleosides (2\'-F-RNA) find constantly increasing applications in research and new drug development. Among important areas of their application are such as design and synthesis of efficient and stable siRNAs, aptamers, anti-microRNAs (Antagomirs) as well as general use for affinity purification of RNA-binding proteins. Today Metkinen Chemistry offers more than 99% pure purine 2\'-fluoronucleosides, prepared by bioconversion of synthetic 2\'-F-uridine, using evolved recombinant E.coli strains. These strains, in turn are grown on the media, incorporation only ingredients, derived from yeast and vegetable. That means that in the production process no secondary reagents of animal source (either BSE certified or non- BSE certified) are employed at any stage of 2\'-F- A and G preparation. Hence, we guarantee the complete absence of ANY BSE/TSE risk, associated with our 2\'-F-nucleosides and derivatives. In addition to purine 2\'-F-nucleosides, we offer a full set of 2\'-F-nucleoside CE-phosphoramidites for chemical synthesis and a full set of 2\'-F-nucleoside 5\'-triphosphates for enzymatic preparation of 2\'-F-RNA. Our latest addition to series of 2\'-fluoronucleoside derivatives - 2\'-F-nucleoside bound solid supports for 2\'-F-RNA oligosynthesis, complements the range of these compounds and opens up a full spectrum of 2\'-F-RNA applications. 2\'-Fluoro modifications consistently provided increased target binding affinity, endonuclease stability, and, importantly, reduced immune response. In addition, it is the only modification compared to other carbohydrate modifications, including locked nucleic acid, or LNA, that preserves RISC activity when used in both sense and antisense strands.Recently, it was also demonstrated that chemical modification of the RNA, employing 2’-F-nucleosides are compatible with Cas9 enzyme activity. This fact will help to guide CRISPR-Cas9 engineering and enable new or improved applications.2\'-Deoxy-2\'-fluoroguanosine2\'-Deoxy-2\'-fluoroadenosine2\'-Deoxy-2\'-fluoroguanosine-3\'-CE-phosphoramidite2\'-Deoxy-2\'-fluoroadenosine-3\'-CE-phosphoramidite2\'-Deoxy-2\'-fluorouridine-3\'-CE-phosphoramidite 2\'-Deoxy-2\'-fluorocytidine-3\'-CE-phosphoramidite2\'-Fluoroarabinooligonucleotides (FANA) can be used as antisense oligonucleotides, siRNA and aptamers. Today Metkinen Chemistry offers synthetically synthesized pyrimidine 2\'-fluoroarabinonucleosides as well as purine 2\'- fluoroarabinonucleosides, prepared by bioconversion of synthetic 2\'-F-arabinouridine, employing propriarory evolved recombinant E.coli strains. We guarantee the complete absence of ANY BSE/TSE risk, associated with our 2\'-F- fluoroarabinonucleosides. Metkinen Chemistry offers a full set of 2\'-F-nucleoside CE-phosphoramidites for the chemical synthesis and a full set of 2\'-F-nucleoside 5\'-triphosphates for enzymatic preparation of FANA. 9-(2-Deoxy-2-fluoro-ß-D-arabinofuranosyl)adenine (2\'-FANA-A) 9-(2-Deoxy-2-fluoro-ß-D-arabinofuranosyl)-2,6-diaminopurine (FANA-DAP) 9-(2-Deoxy-2-fluoro-ß-D-arabinofuranosyl)guanine (2\'-FANA-G) 9-(2-Deoxy-2-fluoro-ß-D-arabinofuranosyl)hypoxantine (2\'-FANA-I) 1-(2-Deoxy-2-fluoro-ß-D-arabinofuranosyl)cytosine (2\'-FANA-C)1-(2-Deoxy-2-fluoro-ß-D-arabinofuranosyl)uracil (2\'-FANA-U) 1-(2-Deoxy-2-fluoro-ß-D-arabinofuranosyl)thymine (2\'-FANA-T) 9-(2-Deoxy-2-fluoro-ß-D-arabinofuranosyl)-6-thioguanine (FANA-thioG) 2\'-Deoxy-2\'-fluoroarabinoadenosine-3\'-CE-phosphoramidite 2\'-Deoxy-2\'-fluoroarabinoguanosine-3\'-CE-phosphoramidite 2\'-Deoxy-2\'-fluoroarabinouridine-3\'-CE-phosphoramidite 2\'-Deoxy-2\'-fluoroarabinocytidine-3\'-CE-phosphoramidite 2\'-Deoxy-2\'-fluoroarabinothymidine-3\'-CE-phosphoramidite Analogues of Purine nucleosides have potential interest in antiviral research and are indispensable tools in Molecular biology. They are building blocks for the synthesis of pharmaceutical oligonucleotide analogues and initial compounds for preparation of corresponding nucleoside 5\'-di- and triphosphates.Metkinen Universal Support is appropriate for the production of DNA and RNA and modified oligonucleotides from laboratory to industrial scale. It requires fast and mild cleavage conditions. Chemical Phosphorylation Reagent allows convenient purification of oligonucleotide 5\'-phosphates by the straightforward DMTr-on technique.Metkinen Chemistry uses proprietary technology for production of some reagents for DNA and RNA synthesis. The invention (CATAPAZ chemistry) relates to highly efficient and straightforward carbamoylation of amines, mercaptanes, thiophenols and some alcohols employing organic azides, triphenylphosphine or polymer bound triphenylphosphine along with aqueous hydrogen carbonate buffer. At present, the CATAPAZ chemistry is successfully used for the production of Universal solid support and new nucleoside bound supports for synthesis of DNA, RNA, siRNA as well as any type of modified oligonucleotides. Development of new products for oligonucleotide synthesis, that are prepared employing the CATAPAZ chemistry is now in progress. Catapaz Patents: A. Yagodkin, A. Azhayev “Carbamoylation of Amines, Thiophenols, Mercaptanes and Phenols employing Organic Azides” United States Patent No. 8,779,194, July 15, 2014; International European Patent No. 2076488; Canadian Patent 2,667,714. Please follow the link to see patent description.Comprehensive coverage of CATAPAZ technology and application can be found in the following articles:1. Tetrahedron, Volume 66, Issue 12, 20 March 2010, Pages 2210-22212. Nucleosides, Nucleotides and Nucleic Acids (2011), 30:7-8, 475-489Trinucleotide phosphoramidite building blocks are reagents of choice for generation of highly randomized DNA sequences. These sequences may incorporate codons and anticodons, corresponding to all natural amino acids. Today all 25 Trimer (codon and anticodon phosphoramidites are available from Metkinen Chemistry. In addition, we are ready to perform Trinucleotide (TRIMER CODON and ANTICODON) PhosphoramiditesCUSTOM SYNTHESIS OF RANDOMIZED OLIGONUCLEOTIDE LIBRARIES GENERATED BY USING TRIMER PHOSPHORAMIDITESAdvantages of using Trimer phosphoramidites for generation of oligonucleotide libraries:Absence of synonymous, rare and stop codonsFare frame-shift mutationsHigh Library variabilityEasily controlled occurrence of each amino acid at certain position Modified Nucleoside 5\'-triphosphates are popular products for various applications: PCR, DNA- and RNA-polymerase, reverse transcriptase based assays, etc. Nowadays these compounds find diverse use in siRNA and Aptamer research.3\'-Amino-2\',3\' dideoxynucleosides are synthesized via biotransformation and used as initial compounds for preparation of corresponding 3\'-Amino-2\',3\'-Dideoxynucleoside-5\'-CE Phosphoramidites. The latter are building blocks for the assembly of Oligonucleotide N3\' -> P5\' phosphoramidates, that form extremely stable double and triple stranded complexes with DNA and RNA under physiological conditions and appear to be efficient telomerase inhibitors and antisense agents.3\'-Amino-3\' deoxynucleosides are synthesized via biotransformation and used as initial compounds for preparation of corresponding 3\'-Amino-3\'-Deoxynucleoside-5\'-CE Phosphoramidites. The latter are building blocks for the assembly of RNA Oligonucleotide N3\' -> P5\' phosphoramidates Phone: +358 40 736 4885, +358 40 554 2218.E-mail: info@metkinenchemistry.com