Hence, the pilicides block the formation of pili by preventing a DSE reaction. Pilicides bind to the hydrophobic patch of residues located in the F1, C1, D1 region of the N-terminal domain conserved in all chaperones [23]. This region encompasses part of the F1-G1 loop which is structurally rearranged during the formation Androgen Receptor antagonist of the chaperone-subunit complex (DSC reaction). The dynamic nature of this region is also reflected in the pilicide binding modes observed in the crystal structures of the pilicide in the complex with a free PapD chaperone

or the PapD-PapH complex [23, 24]. Although, pilicide interactions with conserved I93, located at the end of the β-strand F1, with L32 and with the V56 patch are preserved in these two structures, the electrostatic interactions between R96, located within the loop F1-G1, and R58 residues and carboxyl and carbonyl groups of pilicide are broken as a consequence of the PapH binding to the PapD [24]. The important differences in the structure of the F1-G1 hairpin and the mechanism of

DSC reaction observed between the FGS and FGL assembly systems might potentially affect pilicide binding. This gives rise to the question as to whether pilicides that were originally designed on the basis of the structure of the FGS-type PapD and FimC chaperones and were evaluated as inhibitors of the biogenesis of the P and type 1 pili are also active in respect of the FGL

assembly pathway. In this study, we GSK1120212 chemical structure addressed a question denoting the activity of pilicides Capmatinib manufacturer as inhibitors of the assembly of the Dr fimbriae encoded by the dra operon of uropathogenic E. coli – the model of the FGL-type adhesive structures [25, 26]. These organelles are homopolymers of a single DraE subunit, the structure Edoxaban of which has three receptor binding sites interacting with the following host-cell molecules: Dra blood-group antigen presented on the CD55/decay-accelerating factor (DAF), the carcinoembryonic antigen (CEA)-related cellular adhesion molecules and the 7S domain of basement membrane protein type IV collagen [27–29]. The assembly of Dr fimbriae is dependent on the action of the DraB chaperone and the DraC usher [17]. The data presented in this article are also important from the epidemiology point of view, as uropathogenic E. coli Dr+ strains are responsible for 20–25% of cases of cystitis and 30% of pyelonephritis in pregnant woman [30]. Methods General synthesis of pilicides The reagents were purchased from Sigma-Aldrich. The analytical TLC was performed on aluminum sheets of silica gel UV-254 (Merck). The flash chromatography was carried out using Zeochem silica gel with particle size of 40–63 microns. The NMR spectra 1H and 13C were recorded at Varian Gemini 200 and Varian Unity Plus 500 in CDCl3 or DMSO. The melting points are uncorrected.