 |
 |
 |
|
|||
 |
|||
|
3'-Amino-2',3'-Dideoxynucleoside-5'-CE Phosphoramidites Catalogue numbers: (3'-NH2-dT-CE Phosphoramidite) (3'-NH2-ddG-CE Phosphoramidite) (3'-NH2-ddA-CE Phosphoramidite) (3'-NH2-dd(5-Me-C)-CE Phosphoramidite) Description: amorphous white to off-white solids Purity: >=95% (RP HPLC &31P-NMR) Storage of dry compound: 1 year at -20ºC During last decade, the oligonucleotide N3' –> P5' phosphoramidites attract much attention owing to their very interesting physico-chemical and biological properties [1,2]. These oligonucleotides form very stable duplexes with complimentary native phosphodiester DNA and exceptionally stable duplexes with RNA strands. Moreover, the phosphoramidate compounds form extremely stable triple stranded complexes with single or double stranded DNA oligomers under near physiological salt and pH conditions. They are resistant to enzymatic digestion by nucleases both in vitro and in vivo. Oligonucleotide phosphoramidites apparently are cell permeable, and they have a good bioavailability and biodistribution, while being non-toxic at therapeutically relevant doses. Finally, oligonucleotide phosphoramidites are efficient telomerase inhibitors. Human telomerase is a unique reverse transcriptase that is expressed in multiple cancers, but not in the vast majority of normal cells. It has been proposed that the specific inhibition of telomerase activity in tumors might have significant beneficial therapeutic effects [3]. Central hurdle for the wide use of 3'-amino2,3'-dideoxynucleoside 5'-phosphoramidites for the preparation of oligonucleotide N3' –> P5' phosphoramidites [4], always consisted of the availability of the parent purine 3'-amino-2,3'-dideoxynucleoside. Recently, this problem was successfully solved by elaboration of biocatalytic synthesis of purine aminodideoxy nucleosides on a large scale (5). We now offer monomers of 3'-Amino-2',3'-dideoxynucleosides for the solid phase chemical synthesis of oligonucleotide N3' –> P5' phosphoramidites. These products are subject to proprietary rights of Geron Corporation and are synthesized and sold under the following licensed patents: US 5,859,233; WO 2006/014387; US 11/173,311; US 5,824,793; US 5,726, 297; US 5,837,835. This intellectual property is licensed to Metkinen Chemistry for production and sale for research purposes only. There is no implied license hereunder for any commercial use. 1. Gryaznov, S.M. Oligonucleotide N3'-->P5' phosphoramidites as potential therapeutic agents. Biochim. Biophys. Acta. 1999, 1489, 131-40. 2. Shea-Herbert, B.; Pongracz, K.; Shay, J.W.; Gryaznov, S.M. Oncogene 2002, 21, 638-642. 3. Patents claimed the synthesis of oligonucleotide phosphoramidites and their possible areas of applications are: Lynx Therapeutics Inc. (USA): JP 2003012688; US 6,169,170; US 5,965,720; AU 704,549; PL 328,639; US 5,859,233; EPO 882,059; US 5, 837,835; US 5,726,297; US 5,684,143; AU 6,178,996; WO 9,737,691; HU 76,094; CZ 9,602,745; US 5,631,135;US 5,599,922; US 5,591,607; WO 9,525,814; EPO 754,242; AU 2,190,095. 4. Zielinska, D., Pongracz, K., Gryaznov, S. Tetrahedron Lett. 2006, 47, 4495-4499. 5. Metkinen Chemistry (Finland): US patent Application No. 60/718,722. |
|
|
