49717-85-3Relevant articles and documents
Substitution of adenine by purine-2,6-diainine improves the nonenzymatic oligomerization of ribonucleotides on templates containing thymidine
Hartel, Christian,Goebel, Michael W.
, p. 2541 - 2549 (2000)
A standard DNA sequencer was used as a novel and highly efficient tool to study the template-controlled polymerization of RNA. When labeled with appropriate fluorescent dyes, primers and their extension products could be separated and quantified with excellent sensitivity, reproducibility, and speed. The new technique was applied to compare the template-controlled incorporation of adenosine mononucleotide 2 and its purine-2,6-diamine analogue 3, the latter being capable of forming three H-bonds with thymidine or uridine residues. The rates and yields of incorporation are similar when only one thymidine unit is available for pairing in the template (see template 6 and Table 2). However, on template 7 with two consecutive thymidine residues, purine-2,6-diamine is clearly ahead of adenine (see Table 3). This advantage is most pronounced when the template contains stretches of three and four thymidine moieties (see templates 8 and 9 and Tables 4 and 5, resp.).
Identification of critical ligand binding determinants in Mycobacterium tuberculosis adenosine-5′-phosphosulfate reductase
Hong, Jiyoung A.,Bhave, Devayani P.,Carroll, Kate S.
experimental part, p. 5485 - 5495 (2010/06/19)
Mycobacterium tuberculosis adenosine-5′-phosphosulfate (APS) reductase is an iron-sulfur protein and a validated target to develop new antitubercular agents, particularly for the treatment of latent infection. To facilitate the development of potent and specific inhibitors of APS reductase, we have probed the molecular determinants that underlie binding and specificity through a series of substrate and product analogues. Our study highlights the importance of specific substitutent groups for substrate binding and provides functional evidence for ligand-specific conformational states. An active site model has been developed for M. tuberculosis APS reductase that is in accord with the results presented here as well as prior structural data reported for Pseudomonas aeruginosa APS reductase and related enzymes. This model illustrates the functional features required for the interaction of APS reductase with a ligand and provides a pharmacological roadmap for the rational design of small molecules as potential inhibitors of APS reductase present in human pathogens, including M. tuberculosis.
