Synthesis and Biological Activity of 4′-Thionucleosides of 2-Chloroadenine1

Abstract

1,2,3,5-Tetra-O-acetyl-4-thio-D-riboruranose, prepared from 2,3,5-tri-O-benzyl-D-ribofuranose in four steps, was converted to the corresponding 2-chloroadenine nucleoside (8), which was deoxygenated to obtain 2-chloro-2′-deoxy-4′-thioadenosine (12). This is the first report of a 2′-deoxy-4′-thioribonucleoside of a purine rather than a pyrimidine. These novel nucleosides (8 and 12) were cytotoric to several human tumor cell lines in culture.     

Gene Therapy of Cancer: Activation of Nucleoside Prodrugs with E. coli Purine Nucleoside Phosphorylase

Abstract

During the last few years, many gene therapy strategies have been developed for various disease targets. The development of anticancer gene therapy strategies to selectively generate cytotoxic nucleoside or nucleotide analogs is an attractive goal. One such approach involves the delivery of herpes simplex virus thymidine kinase followed by the acyclic nucleoside analog ganciclovir. We have developed another gene therapy methodology for the treatment of cancer that has several significant attributes. Specifically, our approach involves the delivery of E. coli purine nucleoside phosphorylase, followed by treatment with a relatively non-toxic nucleoside prodrug that is cleaved by the enzyme to a toxic compound. This presentation describes the concept, details our search for suitable prodrugs, and summarizes the current biological data.     

Description of Euroleptochromus gen.n. (Coleoptera,Staphylinidae, Scydmaeninae) from Baltic amber,with discussion of biogeography and mouthpart evolution within Clidicini

A new extinct species of the ant‐like stone beetle supertribe Mastigitae, Euroleptochromus sabathi gen. & sp.n. is described from Eocene Baltic amber. A phylogenetic analysis of Clidicini, with representatives of Leptomastacini and Mastigini as out‐group taxa, provided strong support for a sister‐group relationship between the Neotropical Leptochromus and the new genus. The monophyly of Clidicini is questioned because of an alternative placement of Nearctic Papusus as a sister taxon to Leptomastacini + [Clidicus + (Palaeoleptochromus + (Euroleptochromus + Leptochromus))]. A dispersal‐vicariance analysis provided three alternative scenarios for the evolution of Mastigitae; with Laurasia as the ancestral area of the supertribe, major branching events occurring within either Eurasia or Laurentia and two trans‐Beringia dispersals in Late Cretaceous and Eocene. Euroleptochromus, Palaeoleptochromus and Leptochromus share highly derived structures on postgenae and maxillary palps, probably as part of a specialised feeding or prey capture mechanism. The formation of these modifications in Clidicini is demonstrated to involve a process (traced back to the Campanian, 79 Ma) of elongation and narrowing of maxillary palps and forming a cuticular setal projection from a broadened insertion site of sensory setae.