The HIV-1 frameshift-stimulating (FSS) RNA, a regulatory RNA of critical importance in the virus’ life cycle, has been posited as a novel target for anti-HIV drug development. We report the synthesis and evaluation of triazole-containing compounds able to bind the FSS with high affinity and selectivity. Readily accessible synthetically, these compounds are less toxic than previously reported olefin congeners. We show for the first time that FSS-targeting compounds have antiviral activity against replication-competent HIV in human cells, including a highly cytopathic, multidrug-resistant strain. These results support the viability of the HIV-1 FSS RNA as a therapeutic target and more generally highlight opportunities for synthetic molecule-mediated interference with protein recoding in a wide range of organisms.

Antibacterial copper−hydroxyapatite (Cu−HA) composite coatings on titanium were synthesized using a novel process consisting of two consecutive electrochemical reactions. In the first stage, HA nanocrystals were grown on titanium using the cathodic electrolytic synthesis. The HAcoated titanium was then used as the cathode in a second reaction stage to electrochemically reduce Cu 2+ ions in solution to metallic Cu nanoparticles. Reaction conditions were found that result in nanoscale Cu particles growing on the surface of the HA crystals. The two-stage synthesis allows facile control of copper content in the HA coatings. Antibacterial activity was measured by culturing Escherichia coli (Gram-negative) and Staphylococcus aureus (Gram-positive) in the presence of coatings having varying copper contents. The coatings displayed copper concentration-dependent antibacterial activity against both types of bacteria, likely due to the slow release of copper ions from the coatings. The observation of antibacterial activity from a relatively low loading of copper on the bioactive HA support suggests that multifunctional implant coatings can be developed to supplement or supplant prophylactic antibiotics used in implant surgery that are responsible for creating resistant bacteria strains.

As the importance of RNA as a therapeutic target has become increasingly recognized, the need for new chemotypes able to bind RNA has grown in significance. We hypothesized that diketopiperazines...

A two-stage electrochemical synthesis method was developed to deposit copper nanoparticles onto hydroxyapatite-coated titanium. During the first-stage of electrochemical reaction, a submicron thick hydroxyapatite coating was deposited on the titanium cathode followed by electrochemical reduction of copper ions to form copper nanoparticles on the surface of the hydroxyapatite coating. Reaction parameters, including reaction time, deposition current density, copper ion precursor, and concentration were optimized to uniformly deposit nanosized copper particles. The size of the nanoparticles and overall copper content were controlled by adjusting reaction parameters in the second synthesis stage. This method, therefore, offers a route to adjust copper content in electrolytically deposited hydroxyapatite coatings independently from the hydroxyapatite coating reaction. The morphology and composition of the coatings were examined using scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDS), respectively. The crystalline structure and the surface composition of the material were studied using X-ray powder diffraction (XRD) and X-ray photoelectron spectroscopy (XPS), respectively. The topography and surface roughness of the coatings were measured using atomic force microscopy (AFM). The quantity of copper ions released in the bacterial growth medium was measured using inductively coupled plasma mass spectrometry (ICP-MS) and was associated with the antimicrobial activity of copper-hydroxyapatite coating. Antibacterial properties of these materials were investigated by culturing Escherichia coli (Gram-negative bacteria) and Staphylococcus aureus (Gram-positive bacteria) in the presence of the coatings. The antibacterial effect of the copper-hydroxyapatite coatings was enhanced by increasing the copper content. The data further suggested that the antibacterial activity was a result of the elution of copper ions from the coatings. The copper nanoparticles acted as a reservoir for copper ions, providing sustained antibacterial activity. The incorporation of nanosized copper into bioactive hydroxyapatite coatings will offer protection against post-surgical infection of orthopedic and dental implants, to reduce or eliminate the use of prophylactic antibiotics that are known to cause antibiotic-resistant bacteria strains to develop.