ABSTRACT
A review is devoted to analysis of the prospects of theranostics for multiform glioblastoma with monoclonal antibodies to the epidermal growth factor receptor (EGFR). Treatment of various malignancies demonstrated high potential of the use of EGFR. However, in case of glioblastoma, the effectiveness of monoclonal antibodies to EGFR is constrained by the absence of informative criteria for assessing the effectiveness of diagnosis and treatment of disease.
Subject(s)
Glioblastoma/therapy , Antibodies, Monoclonal , ErbB Receptors , Humans , Theranostic NanomedicineABSTRACT
Aptamers are widely used as molecular recognition elements for detecting and blocking functional biological molecules. Since the common "alphabet" of DNA and RNA consists of only four letters, the chemical diversity of aptamers is less than the diversity of protein recognition elements built of 20 amino acids. Chemical modification of nucleotides enlarges the potential of DNA/RNA aptamers. This review describes the latest achievements in a variety of approaches to aptamers selection with an extended genetic alphabet.
Subject(s)
Aptamers, Nucleotide/chemistry , Nucleotidases/chemistry , SELEX Aptamer Technique , Amino Acids/chemistry , Base Pairing , Click Chemistry , Deoxyribose/chemistry , Oligonucleotides/chemistryABSTRACT
Influenza virus hemagglutinins (HAs) are surface proteins that bind to sialic acid residues at the host cell surface and ensure further virus internalization. Development of methods for the inhibition of these processes drives progress in the design of new antiviral drugs. The state of the isolated HA (i.e. combining tertiary structure and extent of oligomerization) is defined by multiple factors, like the HA source and purification method, posttranslational modifications, pH, etc. The HA state affects HA functional activity and significantly impacts the results of numerous HA assays. In this review, we analyze the power and limitations of currently used HA assays regarding the state of HA.
Subject(s)
Hemagglutinin Glycoproteins, Influenza Virus/chemistry , Hemagglutinin Glycoproteins, Influenza Virus/physiology , Animals , Epitopes/immunology , Hemagglutination Tests , Hemagglutinin Glycoproteins, Influenza Virus/immunology , Humans , Immunologic TechniquesABSTRACT
BACKGROUND: Fibrinogen has been intensively studied with transmission electron microscopy and x-ray diffraction. But until now, a complete 3D structure of the molecule has not yet been available because the two highly flexible αC regions could not be resolved in fibrinogen crystals. This study was aimed at determining whether the αC regions can be visualized by high-resolution atomic force microscopy. METHODS: Atomic force microscopy with super high resolution was used to image single molecules of fibrinogen and fibrin associates. The key approach was to use a graphite surface modified with the monolayer of amphiphilic carbohydrate-glycine molecules and unique supersharp cantilevers with 1 nm tip diameter. RESULTS: Fibrinogen αC regions were visualized along with the complete domain structure of the protein. In almost all molecules at pH 7.4 the D domain regions had one or two protrusions of average height 0.4 ± 0.1 nm and length 21 ± 6 nm. The complex, formed between thrombin and fibrinogen, was also visualized. Images of growing fibrin fibers with clearly visible αC regions have been obtained. CONCLUSIONS: Fibrin αC regions were visible in protofibrils and large fibers; αC regions intertwined near a branchpoint and looked like a zipper. These results support the idea that αC regions are involved in the thickening of fibrin fibers. In addition, new details were revealed about the behavior of individual fibrin molecules during formation of the fibrin network. Under the diluted condition, the positioning of the αC regions could suggest their involvement in long-range interactions between fibrin but not fibrinogen molecules.
