Purchase, NY, United States
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Upadhayaya R.,TAL International | Deshpande S.G.,TAL International | Li Q.,Uppsala University | Kardile R.A.,TAL International | And 7 more authors.
Journal of Organic Chemistry | Year: 2011

Using the intramolecular 5-exo-5-hexenyl radical as a key cyclization step, we previously reported an unambiguous synthesis of carba-LNA thymine (cLNA-T), which we subsequently incorporated in antisense oligonucleotides (AON) and investigated their biochemical properties [J. Am. Chem. Soc.2007, 129 (26), 8362-8379]. These cLNA-T incorporated oligos showed specific RNA affinity of +3.5-5 °C/modification for AON:RNA heteroduplexes, which is comparable to what is found for those of LNAs (Locked Nucleic Acids). These modified oligos however showed significantly enhanced nuclease stability (ca. 100 times more) in the blood serum compared to those of the LNA modified counterparts without compromising any RNase H recruitment capability. We herein report the synthesis of 5-methylcytosine-1-yl (MeC), 9-adeninyl (A), and 9-guaninyl (G) derivatives of cLNA and their oligonucleotides and report their biochemical properties as potential RNA-directed inhibitors. In a series of isosequential carba-LNA modified AONs, we herein show that all the cLNA modified AONs are found to be RNA-selective, but the magnitude of RNA-selectivity of 7′-R-Me-cLNA-G (cLNA-G) (ΔTm = 2.9 °C/modification) and intractable isomeric mixtures of 7′-(S/R)-Me-cLNA-T (cLNA-T, ΔTm = 2.2 °C/modification) was found to be better than diastereomeric mixtures of 7′-(S/R)-Me-cLNA-MeC with trace of cENA-MeC (cLNA-MeC, ΔTm = 1.8 °C/modification) and 7′-R-Me-cLNA-A (cLNA-A, ΔTm = 0.9 °C/modification). cLNA-MeC modified AONs however exhibited the best nuclease stability, which is 4-, 7-, and 20-fold better, respectively, than cLNA-T, cLNA-A, and cLNA-G modified counterparts, which in turn was more than 100 times stable than that of the native. When the modification sites are appropriately chosen in the AONs, the cLNA-A, -G, and -MeC modified sites in the AON:RNA hybrids can be easily recognized by RNase H, and the RNA strand of the hybrid is degraded in a specific manner, which is important for the design of oligos for therapeutic purposes. The cLNA-MeC modified AON/RNA, however, has been found to be degraded 4 times faster than cLNA-A and G modified counterparts. By appropriately choosing the carba-LNA modification sites in AON strands, the digestion of AON:RNA can be either totally repressed or be limited to cleavage at specific sites or at a single site only (similar to that of catalytic RNAzyme or DNAzyme). Considering all physico- and biochemical aspects of cLNA modified oligos, the work suggests that the cLNA modified antisense oligos have the potential of being a promising therapeutic candidate due to their (i) higher nucleobase-specific RNA affinity and RNA selectivity, (ii) greatly improved nuclease stability, and (iii) efficient RNase H recruitment capability, which can induce target RNA cleavage in a very specific manner at multiple or at a single site, in a designed manner. © 2011 American Chemical Society.


Patent
TAL International | Date: 2010-08-11

A securement device is provided for securing articles such as collapsed shipping racks together for maintaining their stability and alignment. The device includes a tether that is connectable between adjacent shipping racks to secure the racks together, and that provides a clear visual indication that the racks are secured. A securement device affixed to a collapsible shipping rack may further comprise a bracket member and upper and lower pin members coupled to the bracket member, with the tether having first and second opposite end portions and the first end portion of the tether being coupled to one of the upper and lower pin members, and the second end portion being releasably attachable to another securement device of another collapsible shipping rack adjacently stacked relative to the first collapsible shipping rack.


TAL International | Entity website

Select a RegionNORTH AND SOUTH AMERICA EASTERN CARIBBEAN CENTRAL CANADA GULF SOUTH AMERICA WEST COAST BURLINGTON NORTHERN - CICEROEUROPE UNITED KINGDOM SCANDINAVIA GERMANY BENELUX MEDITERRANEAN SOUTH AFRICANORTH AND SOUTH PACIFIC JAPAN AUSTRALIA FAR EAST SOUTH EAST ASIAAll Ports in this Region


TAL International | Entity website

FlatRack Containers FLATRACKS Not everything fits neatly into a box. Our FLATRACK specials incorporate the newest technology and safety features to accommodate easy loading and unloading, and secure transporting of odd-shaped cargo ...


TAL International | Entity website

OpenTop Containers OPEN TOPS Flexibility and functionality merge in the design of our OPEN TOP specials, and we have the worlds largest fleet at your disposal. Now theres no need to sacrifice convenience or compromise safety simply because your cargo requires the leeway of an open-top container ...


TAL International | Entity website

Select a Region NORTH AND SOUTH AMERICA EASTERN CARIBBEAN CENTRAL CANADA GULF SOUTH AMERICA WEST COAST BURLINGTON NORTHERN - CICERO EUROPE UNITED KINGDOM SCANDINAVIA GERMANY BENELUX MEDITERRANEAN SOUTH AFRICA NORTH AND SOUTH PACIFIC JAPAN AUSTRALIA FAR EAST SOUTH EAST ASIA All Ports in this Region


TAL International | Entity website

TAL International is one of the world's oldest and largest lessors of intermodal freight containers. We were founded in 1963 soon after the development of containerized trade, and today we serve virtually every major shipping line in the world ...


TAL International | Entity website


HAMILTON, Bermuda--(BUSINESS WIRE)--Triton International Limited (NYSE:TRTN), ("Triton") today reported results for the third quarter ended September 30, 2016. On July 12, 2016 Triton Container International Limited ("TCIL") and TAL International Group, Inc. ("TAL") completed their previously announced strategic combination and became wholly-owned subsidiaries of Triton. In this press release, Triton has presented its results based on U.S. GAAP as well as Non-GAAP selected information for the t

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