Interactions of 2,6-substituted purines with purine nucleoside phosphorylase from Helicobacter pylori in solution and in the crystal,and the effects of these compounds on cell cultures of this bacterium

Helicobacter pylori represents a global health threat with around 50% of the world population infected. Due to the increasing number of antibiotic-resistant strains, new strategies for eradication of H. pylori are needed. In this study, we suggest purine nucleoside phosphorylase (PNP) as a possible new drug target, by characterising its interactions with 2- and/or 6-substituted purines as well as the effect of these compounds on bacterial growth. Inhibition constants are in the micromolar range, the lowest being that of 6-benzylthio-2-chloropurine. This compound also inhibits H. pylori 26695 growth at the lowest concentration. X-ray structures of the complexes of PNP with the investigated compounds allowed the identification of interactions of inhibitors in the enzyme’s base-binding site and the suggestion of structures that could bind to the enzyme more tightly. Our findings prove the potential of PNP inhibitors in the design of drugs against H. pylori.     

Lipopolysaccharide structures of Helicobacter pylori wild-type strain 26695 and 26695 HP0826::Kan mutant devoid of the O-chain polysaccharide component

We describe a re-investigation of the structure of the lipopolysaccharide (LPS) from Helicobacter pylori genomic strain 26695 and its corresponding HP0826::Kan mutant lacking the O-chain component based on the in-depth NMR analysis of the oligosaccharide products obtained through the use of various degradation procedures performed on the purified LPS from both strains, as well as CE–MS data. New structural evidence indicates the presence of the linear arrangement of glucan and heptan portions of the LPS attached through -6-α-ddHep-3-α-l-Fuc-3-β-GlcNAc- fragment to the inner core dd-heptose residue. This structure differs from previously reported structures of the H. pylori 26695 LPS in several aspects.