Institute of
bioorganic chemistry

Carriers providing active targeted delivery of anticancer drugs to tumor cells are promising for cancer chemotherapy. A team of scientists from the IBCh RAS in collaboration with collegues from other Russian Institutes have developed biodegradable polyelectrolyte microcapsules which have been modified with the DR5-B ligand. The latter is a promising recombinant analogue of the cytokine TRAIL (tumor necrosis factor-related apoptosis-inducing ligand), which specifically binds to the DR5 death receptor overexpressed on the tumor (but not normal) cell membrane. In addition, the capsules were loaded with the anticancer drug doxorubicin (DOX) in a subtoxic concentration. The capsules were demonstrated to provide a targeted drug delivery to tumor cells, as well as a synergistic anticancer effect. The results are published in Nanomaterials. Learn more

Human InsR, IGF1R, and IRR receptor tyrosine kinases of the insulin receptor subfamily play an important role in signaling pathways for a wide range of physiological processes. Sharing high sequence and structure homology, the receptors differ dramatically in their localization, expression, and functions. A team of scientists from IBСH RAS in cooperation with colleagues from other institutions using the high-peroscopy of high resolution and computer modeling established that the conformational variability of transmembrane domains and their interaction with surrounding lipids differ significantly among representatives of the subfamily. Thus, the heterogeneous membrane environment should be taken into account in the diverse activation mechanisms of InsR, IGF1R, and IRR. This membrane-mediated control of receptor signaling offers an attractive prospect for the development of new targeted therapies for diseases associated with dysfunction of insulin subfamily receptors. The results are published in the International Journal of Molecular Sciences. Learn more

Scientists from IBCH RAS, together with colleagues from the Federal Research Center for Physical and Chemical Medicine and other Russian institutes, have developed a platform for fluorescent imaging of small non-coding RNAs (sncRNAs) in living cells. The system consists of a fluorogenic cyanine dye and a genetically encoded Mango II aptamer-based label, which is attached to the sncRNA of interest and causes an increase in dye fluorescence upon complex formation. An approach to optimizing the spectral properties of dyes was proposed and a minimal genetically encoded label (52 nt) for sncRNA visualization was developed. The applicability of the system for intracellular imaging and tracking of sncRNA was verified using an intracellular internalization of Mycobacterium smegmatis by a host macrophage. The work was published in Nucleic Acids Research.

A group of scientists from the Laboratory of Molecular Biophysics and the Laboratory of Carbohydrates of the IBCH RAS, the A.V. Shubnikov Institute of Crystallography, and the European Molecular Biology Laboratory (Hamburg) developed a new approach to study the structure of nanoparticles by combining SAXS and molecular dynamics. In their paper, published in Colloids and Surfaces B: Biointerfaces, they characterized the surface structure of core-shell nanoparticles formed by biotin-CMG2-DOPE amphiphil using SAXS contrast variation and low-resolution Ab initio structure restoration. This approach demonstrates heterogeneity of the nanoparticles surface through a non-uniform distribution of the polar CMG2 spacer around the nonpolar core, localized in the form of patches. The data were verified by comparing with all-atom nanoparticle structure obtained from molecular dynamics simulation, indicating the efficacy of SAXS contrast variation to assess surface structure heterogeneity of multi-phase nanoparticles. Learn more

In birch-dominated areas, sensitization of the human immune system to pollen from trees of the order Fagales is considered to be initiated by the major birch pollen allergen Bet v 1. A collaboration of scientists from the Science-Educational center of the IBCh RAS and the Center for Pathophysiology, Infectology and Immunology of the Medical University of Vienna proved that the humoral and cellular response of the human immune system to pollen allergens from trees of the order Fagales is not mediated by cross-reactivity with the birch pollen Bet v 1, but indicates the existence of Bet v 1-independent sensitization in individuals from birch tree-dominated areas. This study has been published in Allergy. Learn more