847-21-2

Upstream product

• 90729-89-8 (3'-amino-3'-deoxythymidylyl)-(3'->5')-thymidine 
• 70900-93-5 P,P-dithio-[5']thymidylic acid S,S'-diphenyl ester 

Relevant academic research and scientific papers

Stereochemistry of internucleoside phosphorus atom affects sugar pucker and acid hydrolysis of N3′-P5′ thio-phosphoramidates

Investigation of the sugar pucker of the two diastereomers of dinucleotide N3′-P5′-thio-phosphoramidates TNPSTNH2 and TNPSTOH shows that the Sp isomer adopts a more C3′-endo (North) sugar ring configuration than the Rp counterpart. In contrast, P-stereochemistry of oligonucleotide phosphorothioate (O3′-P5′) compounds has no effect on the nucleoside sugar puckering. This difference is also reflected in the different rate of acid hydrolysis for the two isomers. Thus, the Rp stereoisomer with less prevalent C3′-endo configuration has an acid hydrolysis rate constant ~50% higher than that of the Sp molecule. The TNPOTNH2 and TNPOTOH dinucleotides are hydrolyzed an order of magnitude faster than TNPSTNH2 and TNPSTOH, respectively. In addition, dinucleotides with the terminal 3′-OH group are hydrolyzed two times faster than their 3′-NH2 counterparts.

Histidine triad nucleotide-binding proteins HINT1 and HINT2 share similar substrate specificities and little affinity for the signaling dinucleotide Ap4A

Human histidine triad nucleotide-binding protein 2 (hHINT2) is an important player in human mitochondrial bioenergetics, but little is known about its catalytic capabilities or its nucleotide phosphoramidate prodrug (proTide)-activating activity akin to the cytosolic isozyme hHINT1. Here, a similar substrate specificity profile (kcat/Km) for model phosphoramidate substrates was found for hHINT2 but with higher kcat and Km values when compared with hHINT1. A broader pH range for maximum catalytic activity was determined for hHINT2 (pK1?=?6.76?±?0.16, pK2?=?8.41?±?0.07). In addition, the known hHINT1-microphthalmia-inducing transcription factor-regulating molecule Ap4A was found to have no detectable binding to HINT1 nor HINT2 by isothermal titration calorimetry. These results demonstrate that despite differences in their sequence and localization, HINT1 and HINT2 have similar nucleotide substrate specificities, which should be considered in future proTide design and in studies of their natural function.

Synthesis and Properties of S,S-Diaryl Thymidine Phosphorodithioates

Appropriately protected and unprotected S,S-diphenyl thymidine 3'- or 5'-phosphorodithioates and S,S-bis(4-methoxyphenyl) thymidine 3'- or 5'-phosphorodithioates were successfully prepared by the reaction of the thymidine derivatives with cyclohexylammoni