19083-35-3

Upstream product

• 7226-75-7 5-benzyloxymethyl-3',5'-di-O-toluoyl-2'-deoxyuridine 
• 1028383-90-5 N³-tert-butyloxycarbonyl-5-bromomethyl-3',5'-bis-O-tert-butyldimethylsilyl-2'-deoxyuridine 
• 100-51-6 benzyl alcohol 
• 304849-80-7 5-[(benzyloxy)methyl]-3',5'-O-(1,1,3,3-tetraisopropyldisiloxane-1,3-diyl)uridine 
• 13111-67-6 2',3',5'-tri-O-acetyl-5-[(benzyloxy)methyl]uridine 
• 24751-66-4 5-[(benzyloxy)methyl]uridine 
• 98808-20-9 O,O'-bis(trimethylsilyl)-5-benzyloxymethyluracil 
• 4330-34-1 methyl 3,5-di-O-toluoyl-2-deoxy-D-ribofuranose 
• 304849-81-8 5-[(benzyloxy)methyl]-2'-deoxy-3',5'-O-(1,1,3,3-tetraisopropyldisiloxane-1,3-diyl)uridine 
• 13035-61-5 1,2,3,5-tetraacetylribose 
• 7295-02-5 benzyl hydroxymethyl uridine 

Downstream Products

• 304849-85-2 5-[(benzyloxy)methyl]-2'-deoxy-5'-O-(4,4'-dimethoxytrityl)uridine 
• 50-89-5 thymidine 
• 304849-87-4 5-benzyloxymethyl-5'-O-(4,4'-dimethoxytrityl)-2'-deoxyuridine 3'-(N,N-diisopropyl)-2-cyanoethyl phosphoramidite 

Relevant academic research and scientific papers

Base-modified thymidines capable of terminating DNA synthesis are novel bioactive compounds with activity in cancer cells

Current FDA-approved chemotherapeutic antimetabolites elicit severe side effects that warrant their improvement; therefore, we designed compounds with mechanisms of action focusing on inhibiting DNA replication rather than targeting multiple pathways. We previously discovered that 5-(α-substituted-2-nitrobenzyloxy)methyluridine-5′-triphosphates were exquisite DNA synthesis terminators; therefore, we synthesized a library of 35 thymidine analogs and evaluated their activity using an MTT cell viability assay of MCF7 breast cancer cells chosen for their vulnerability to these nucleoside derivatives. Compound 3a, having an α-tert-butyl-2-nitro-4-(phenyl)alkynylbenzyloxy group, showed an IC50 of 9 ± 1 μM. The compound is more selective for cancer cells than for fibroblast cells compared with 5-fluorouracil. Treatment of MCF7 cells with 3a elicits the DNA damage response as indicated by phosphorylation of γ-H2A. A primer extension assay of the 5′-triphosphate of 3a revealed that 3aTP is more likely to inhibit DNA polymerase than to lead to termination events upon incorporation into the DNA replication fork.

Nucleotides and nucleosides and methods for their use in DNA sequencing

The present invention relates generally to labeled and unlabled cleavable terminating groups and methods for DNA sequencing and other types of DNA analysis. More particularly, the invention relates in part to nucleotides and nucleosides with chemically cleavable, photocleavable, enzymatically cleavable, or non-photocleavable groups and methods for their use in DNA sequencing and its application in biomedical research.

Preparation of oligodeoxynucleotides containing 5-(N-methylpiperazinyl) and 5-benzyloxymethyl uracils

Deprotected compounds 1 and 9 were allowed to react with 4,4'-dimethoxytrityl chloride in pyridine to give 5'-O-DMT nucleosides 2 and 10. The 3'-phosphoramidites 4 and 11 were incorporated into oligodeoxynucleosides (ODNs). The hybridization properties of the modified ODNs with their complementary DNA strands were studied. Interesting results were obtained when 11 was inserted as a bulged nucleoside into TWAs, duplexes, and triplexes.

Aromatic vs. Carbohydrate residues in the major groove: Synthesis of 5-[(benzyloxy)methyl]pyrimidine nucleosides and their incorporation into oligonucleotides

The synthesis of 5-[(benzyloxy)methyl]-substituted pyrimidine 2'-deoxynucleosides 14 and 15 starting from the uracil derivative 6 and tetra-O-acetyl-D-ribose is described (Schemes 1-3). These nucleosides were converted to the corresponding cyanoethyl phosphoramidites 18 and 19, respectively, and incorporated into oligodeoxynucleotide decamers. The 5-[(benzyloxy)methyl]-nucleoside building blocks (bo)T(d) and (bom)C(d) (bo = benzyloxy, bom = (benzyloxy)methyl) - shape analogs of the naturally occurring glucosylated nucleosides 1 and 2 (see Fig. 1) - lead to weaker binding affinities of oligodeoxynucleotides pairing to DNA as well as RNA complements. The modification is more destabilizing in the case of (bo)T(d) than (bom)C(d). Analysis of the thermodynamics of duplex formation shows that (bo)T(d) and (bom)C(d) incorporation leads to a smaller entropy change in duplex formation that is, however, overcompensated by a less favorable enthalpy term. Molecular-modeling studies suggest that the benzyl groups reside in the major groove which would explain the improved pairing entropy as a result of the exclusion of ordered H2O.