Current Pharmaceutical Design - Volume 23, Issue 45, 2017

Nucleosides constitute an extensive group of natural and chemically modified compounds that display a wide range of structures and activities. Different biocatalysts have been developed for their preparation, but the choice of commercially available enzymes is limited. Therefore, the search of new biocatalysts is particularly attractive. In this sense, microorganisms are a vast source of enzymatic diversity that can be di Read More

Background: Nucleoside analogue (NA) derivatives comprise a large family of pharmaceuticals clinically used as antitumoral and antiviral compounds. Originally, the production of NAs involved chemical synthesis, but a greener bioproduction alternative exists and involves the use of enzymes that catalyze transglycosylation reactions between modified purinic or pyrimidinic bases and sugars. To be considered as an op Read More

Background: In recent years, enzymatic methods have shown to be an efficient and sustainable alternative for the synthesis of nucleosides and nucleoside-5'-monophosphates (NMPs) to the traditional multistep chemical methods, since chemical glycosylation reactions include several protection–deprotection steps and the use of chemical reagents and organic solvents that are expensive and environmentally harmful. Read More

Background: Nucleoside phosphorylases catalyze the reversible phosphorolysis of pyrimidine and purine nucleosides in the presence of phosphate. They are relevant to the appropriate function of the immune system in mammals and interesting drug targets for cancer treatment. Next to their role as drug targets nucleoside phosphorylases are used as catalysts in the synthesis of nucleosides and their analogs that are widely ap Read More

Background: Nucleoside 5'-triphosphates (NTPs) play an important role in cells in the transfer of phosphate groups or bioenergy. In vivo, they are ready to be produced, regenerated and consumed in different kinds of metabolic pathways, and their concentrations are strictly controlled. NTPs are useful reagents that take part in many biosynthetic processes. However, NTPs are expensive and unstable, which greatly increases t Read More

Background: Purine-nucleoside phosphorylase (PNP) is known as a tool for the synthesis of various nucleosides and nucleoside analogues. Mechanism, properties, molecular diversity and inhibitors of PNP, particularly these of pharmacological significance, are briefly characterized. Methods: UV and fluorescence spectroscopy was used for kinetic experiments, and HPLC chromatography for product analyses. Results: Read More

Background: Schistosoma mansoni is the etiological agent of schistosomiasis, a debilitating treatment neglected tropical disease that affects approximately 218 million people worldwide. Despite its importance, the treatment of schistosomiasis relies on a single drug, praziquantel. Some reports on the resistance of S. mansoni to this drug have stimulated efforts to develop new drugs to treat this disease. S. mansoni posse Read More

Background: Modified nucleoside and nucleotide analogs are now the cornerstone of antiviral and anticancer chemotherapies. However, these compounds are not active on their own and need, after entering the cell, to be metabolized to their active 5'-triphosphate form. Methods: Limitations of these metabolic processes led to development of nucleoside/nucleotide prodrugs in which nucleosides are masked with dif Read More

Background: The selective expression of non-human genes in tumor tissue to activate non-toxic compounds (Gene Directed Enzyme Prodrug Therapy, GDEPT) is a novel strategy designed for killing tumor cells in patients with little or no systemic toxicity. Numerous non-human genes have been evaluated, but none have yet been successful in the clinic. Methods: Unlike human purine nucleoside phosphorylase (PNP), E. coli P Read More