Detonation nanodiamond (ND) is a suitable source material to produce unique samples consisting of almost uniform diamond nanocrystals (d = 3–5 nm). Such samples exist in the form of long stable aqueous dispersions with narrow size distribution of diamond particles. The material is finding ever increasing application in biomedicine. The major problem in producing monodispersed diamond colloids lies in the necessity of deagglomeration of detonation soot and/or removing of clusters formed by already isolated core particles in dry powders. To do this one must have an effective method to monitor the aggregation state or dispersity of powders and gels prior to the preparation of aqueous dispersions. In the absence of dispersity control at various stages of preparation the reproducibility of properties of existing ND materials is poor. In this paper we introduce differential scanning calorimetry (DSC) as a new tool capable to distinguish the state of aggregation in dry and wetted ND materials and to follow changes in this state under different types of treatment. Samples with identical X-ray diffraction patterns (XRD) and high resolution transmission electron microscopy (HRTEM) images gave visibly different DSC traces. Strong correlation was found between dynamic light scattering (DLS) data for colloids and DSC parameters for gels and powders of the same material. Based on DSC data we improved dispersity of existing ND materials and isolated samples with the best possible DSC parameters. These were true monodispersed easily dispersible fractions of ND particles with diameters of ca. 3 nm.

Chaperonins promote protein folding in vivo and are ubiquitously found in bacteria, archaea, and eukaryotes. The first viral chaperonin GroEL ortholog, gene product 146 (gp146), whose gene was earlier identified in the genome of bacteriophage EL, has been shown to be synthesized during phage propagation in Pseudomonas aeruginosa cells. The recombinant gp146 has been expressed in Escherichia coli and characterized by different physicochemical methods for the first time. Using serum against the recombinant protein, gp146's native substrate, the phage endolysin gp188, has been immunoprecipitated from the lysate of EL-infected bacteria and identified by mass spectrometry. In vitro experiments have shown that gp146 has a protective effect against endolysin thermal inactivation and aggregation, providing evidence of its chaperonin function. The phage chaperonin has been found to have the architecture and some properties similar to those of GroEL but not to require cochaperonin for its functional activity.

Potyviruses represent the most biologically successful group of plant viruses, but to our knowledge, this work is the first detailed study of physicochemical characteristics of potyvirus virions. We measured the UV absorption, far and near UV circular dichroism spectra, intrinsic fluorescence spectra, and differential scanning calorimetry (DSC) melting curves of intact particles of a potato virus A (PVA). PVA virions proved to have a peculiar combination of physicochemical properties. The intravirus coat protein (CP) subunits were shown to contain an unusually high fraction of disordered structures, whereas PVA virions had an almost normal thermal stability. Upon heating from 20°C to 55°C, the fraction of disordered structures in the intravirus CP further increased, while PVA virions remained intact at up to 55°C, after which their disruption (and DSC melting) started. We suggest that the structure of PVA virions below 55°C is stabilized by interactions between the remaining structured segments of intravirus CP. It is not improbable that the biological efficiency of PVA relies on the disordered structure of intravirus CP.

Hsp70 chaperone controls proteostasis and anti-stress responses in rapidly renewing cancer cells, making it an important target for therapeutic compounds. To date several Hsp70 inhibitors are presented with remarkable anticancer activity, however their clinical application is limited by the high toxicity towards normal cells. This study aimed to develop assays to search for the substances that reduce the chaperone activity of Hsp70 and diminish its protective function in cancer cells. On our mind the resulting compounds alone should be safe and function in combination with drugs widely employed in oncology. We constructed systems for the analysis of substrate-binding and refolding activity of Hsp70 and to validate the assays screened the substances representing most diverse groups of chemicals of InterBioScreen library. One of the inhibitors was AEAC, an N-amino-ethylamino derivative of colchicine, which toxicity was two-orders lower than that of parent compound. In contrast to colchicine, AEAC inhibited substrate-binding and refolding functions of Hsp70 chaperones. The results of a drug affinity responsive target stability assay, microscale thermophoresis and molecular docking show that AEAC binds Hsp70 with nanomolar affinity. AEAC was found to penetrate C6 rat glioblastoma and B16 mouse melanoma cells and reduce there the function of the Hsp70-mediated refolding system. Although the cytotoxic and growth inhibitory activities of AEAC were minimal, the compound was shown to increase the antitumor efficiency of doxorubicin in tumor cells of both types. When the tumors were grown in animals, AEAC administration in combination with doxorubicin exerted maximal therapeutic effect prolonging animal survival by 10–15 days and reducing tumor growth rate by 60%. To our knowledge, this is the first time that this approach to the high-throughput analysis of chaperone inhibitors has been applied, and it can be useful in the search for drug combinations that are effective in the treatment of highly resistant tumors.

This review presents the main properties of hydroxycinnamic acid (HCA) derivatives and their potential application as agents for the prevention and treatment of neurodegenerative diseases. It is partially focused on the successful use of these compounds as inhibitors of amyloidogenic transformation of proteins. Firstly, the prerequisites for the emergence of interest in HCA derivatives, including natural compounds, are described. A separate section is devoted to synthesis and properties of HCA derivatives. Then, the results of molecular modeling of HCA derivatives with prion protein as well as with α-synuclein fibrils are summarized, followed by detailed analysis of the experiments on the effect of natural and synthetic HCA derivatives, as well as structurally similar phenylacetic and benzoic acid derivatives, on the pathological transformation of prion protein and α-synuclein. The ability of HCA derivatives to prevent amyloid transformation of some amyloidogenic proteins, and their presence not only in food products but also as natural metabolites in human blood and tissues, makes them promising for the prevention and treatment of neurodegenerative diseases of amyloid nature.