Protein and Peptide Letters - Volume 25, Issue 10, 2018

Background: Monoclonal antibodies have been proven to deliver significant contribution in health industry for the development of both therapeutics and diagnostics. Efforts have been made to achieve immunoglobulin with high antigen specificity and stability. In this regard, smaller fragment of antibody has been constructed as an alternative of full immunoglobulin molecules due to the feasibility of recombinant production in various host cells. Antibody fragments are that part of an immunoglobulin which can form a complete epitope binding site and also retain the binding efficiency and accuracy of a whole antibody. However, the effector functions cannot be accomplished by antibody fragments alone as they lack Fc region. Hence, full antibody is constructed by fusing Fc domain of a human antibody. Nevertheless, to find an antibody with high antigen specificity and stability is still a big challenge. Conclusion: Recent protein engineering techniques have enabled many options of modification and tailoring of antibody fragments for better stability, specificity and pharmacokinetic properties. This review focuses on the latest techniques applied for the construction of antibody fragments, recent developments toward affinity maturation and applications of recombinant antibodies.

Background: Anxiety and mood disorders are the most abundant mental health problems worldwide. The commonly used in clinical practice anxiolytics are focused on pharmacological modulation of brain GABA receptor system activity. As a rule, their use presents a wide spectrum of clinical issues such as dependence, memory impairment and etc. There is an increasing appreciation of the role of neuropeptides and bioactive lipids in the pathophysiology of mood and anxiety disorders as “mild” agents. Heptapeptide Selank (Thr-Lys-Pro-Arg-Pro-Gly-Pro) exhibits prolonged anti-anxiety and nootropic effects. Objective: In this issue, we tried to find the molecular mechanisms which may underlie Selank antianxiety effects. Methods: The main method we used was the radioligand – receptor method of analysis. We also used HPLC (to obtain and ensure reagents and Selank purity) and the methods of brain cells plasmatic membranes isolation and following detection of protein concentration in membrane samples. Results: It was shown that Selank affect the [3H]GABA binding as a positive allosteric modulator. The joint action of Selank and some of benzodiazepines also regulates activity of [3H]GABA binding in specific manner, which is not cumulative and differs from either substance individually. Selank is able to block the modulatory activity of Diazepam and Olanzapine, the location of their and peptide binding sites apparently not the same, but potentially may partially overlaps. Conclusion: Thus, we hypothesized and showed that one of Selank anti-anxiety molecular mechanisms can be associated with subtype selective concentration - dependent allosteric modulation of GABA receptors.

Background: Asthma is the inflammatory disorder of airways highly prevalent in both, children and adults all over the world. The aim of this study was to investigate the serum proteome for the identification of proteins contributing to the pathogenesis of non-atopic asthma. Methods: Protein expression profiling of sera from non-atopic asthmatic patients (n=73) and controls (n=99) was carried out using 1D SDS PAGE. Differentially expressed protein bands were compared with controls, cut from the gel and identified by LC-Q-TOF_MSMS analysis. Results: Various acute phase proteins (i.e., haptoglobin, transthyretin, serum amyloid A, and serum albumin), retinol binding protein 4 (RBP4), Ig gamma-1-chain C-region, hemoglobin subunit β, complement system components (C8 gamma chain and C4-A), ApoA-1 and Ig Κ chain C-region containing protein fractions were predominantly down-regulated in asthmatic patients. Similarly, a higher proportion of male patients exhibited down-regulation of all other (except albumin and C4-A containing) protein fractions as compared to female patients. However, fractions consisting of another acute phase protein, inter-alpha-trypsin heavy chain 4 (ITIH4) and complement system component C3 were up-regulated in the majority of patients. Conclusion: Our study is the first to confirm the role of thyroxine (TTR), retinol (RBP4), cholesterol (apoA-1) transporting proteins, inflammation and its mediators in the pathogenesis of asthma. Further study may help to improve diagnosis and plan better treatment strategies.