Search

Identifying high-affinity antibodies in human serum is challenging due to extremely low number of circulating B cells specific to the desired antigens. Delays caused by a lack of information on the immunogenic proteins of viral origin hamper the development of therapeutic antibodies. We propose an efficient approach allowing for enrichment of high-affinity antibodies against pathogen proteins with simultaneous epitope mapping, even in the absence of structural information about the pathogenic immunogens. To screen therapeutic antibodies from blood of recovered donors, only pathogen transcriptome is required to design an antigen polypeptide library, representing pathogen proteins, exposed on the bacteriophage surface. We developed a two-dimensional screening approach enriching lentiviral immunoglobulin libraries from the convalescent or vaccinated donors against bacteriophage library expressing the overlapping set of polypeptides covering the spike protein of SARS-CoV-2. This platform is suitable for pathogen-specific immunoglobulin enrichment and allows high-throughput selection of therapeutic human antibodies. The authors present a 2D screening approach using antibody libraries against a panel of antigen fragments exposed on the phage surface, which facilitates the mapping of monoclonal antibodies to panels of diverse antigens, even with unknown immunogens. [ABSTRACT FROM AUTHOR]

This document provides information on the synthesis and characterization of several compounds, including 2,3,4,5-tetraphenyl-N-(p-tolyl)-1H-benzo[b]azepine-9-carboxamidecarboxamide (8b), N-(4-chlorophenyl)-2,3,4,5-tetraphenyl-1H-benzo[b]azepine-9-carboxamide (8d), and N-(3-methoxyphenyl)-2,3,4,5-tetraphenyl-1H-benzo[b]azepine-9-carboxamide (8e). The compounds were synthesized using a general procedure and purified using PTLC. The physical and spectroscopic properties of the compounds were determined, including melting point, Rf value, IR, 1H NMR, 13C NMR, and HRMS. The computational methodology used for the study is also mentioned, along with acknowledgments and supporting information. [Extracted from the article]

The possibility of generating azomethine ylides from 11H-benzo[4,5]imidazo[1,2-a]indol-11-one and amino acids is shown for the first time. Based on the cycloaddition reactions of these azomethine ylides with cyclopropenes and maleimides, cyclopropa[a]pyrrolizines, 3-azabicyclo[3.1.0]hexanes, and pyrrolo[3,4-a]pyrrolizines spiro-fused with a benzo[4,5]imidazo[1,2-a]indole fragment were synthesized. Spirocyclic compounds were obtained in moderate to good yields, albeit with poor diastereoselectivity. Density functional theory calculations were performed to obtain an insight into the mechanism of the 1,3-dipolar cycloaddition of 11H-benzo[4,5]imidazo[1,2-a]indol-11-one-derived azomethine ylides to cyclopropenes. The cytotoxic activity of some of the obtained cycloadducts against the human erythroleukemia (K562) cell line was evaluated in vitro by MTS-assay. [ABSTRACT FROM AUTHOR]

3-Aryl-4-hydroxy-1-methyl-3,4-dihydroquinazolin-2(1 H)-ones were synthesized by reduction of 3-aryl-1-methylquinazoline-2,4(1 H ,3 H)-diones with sodium triethylborohydride and studied as precursors of N -acyliminium cations that were expected to be trapped with various alkenes as (4+2)-cycloadducts. Unsubstituted 3-aryl-4-hydroxy-1-methyl-3,4-dihydroquinazolin-2(1 H)-ones in the presence of BF3 ·Et2 O failed to produce the desired cycloadducts probably due to a homooligomerization reaction involving N -acyliminium intermediates. To prevent this side reaction, we found it necessary to introduce substituents at both positions C6 and C8 of the quinazoline ring and C4′ of the 3-phenyl substituent. Utilizing bromine atoms as substituents at C6 and C8, N -acyliminium cations generated from 3-aryl-6,8-dibromo-4-hydroxy-1-methyl-3,4-dihydroquinazolin-2(1 H)-ones in the presence of BF3 ·Et2 O smoothly reacted with such alkenes as indene, acenaphthylene, styrene, α-methylstyrene to give new quinolino[1,2- c ]quinazolin-6-one derivatives with high regio- and stereoselectivity. Density functional theory calculations were performed at the M06-2x/cc-pVDZ level to obtain an insight into the mechanism of the (4+2)-cycloaddition reaction of quinazoline-derived N -acyliminium cations to alkenes. [ABSTRACT FROM AUTHOR]

A diastereoselective synthesis of biologically interesting spirobarbiturates has been achieved via [3+2] cycloaddition of alloxan-derived azomethine ylides to 3- R -1,2-diphenylcyclopropenes. With this approach, a range of spirobarbiturate-3-azabicyclo[3.1.0]hexanes and spirobarbiturate-cyclopropa[ a ]pyrrolizines were obtained in moderate to good yields with excellent diastereoselectivities. DFT calculations (M11 density functional theory) were carried out to shed light on the molecular mechanism of 1,3-dipolar cycloaddition of alloxan-derived azomethine ylides to cyclopropenes. The cytotoxic activity of some obtained compounds against human erythroleukemia (K562) cell line was evaluated in vitro by MTS-assay. [ABSTRACT FROM AUTHOR]

Upon heating methanol solutions, tosylpropadiene cycloadds to proline-derived ylides with the formation of pyrrolidine adducts as single diastereomers in 16–37% yields. The observed diastereo- and regioselectivity is reasoned by a concise DFT study. [ABSTRACT FROM AUTHOR]

A series of heterocyclic compounds containing a spiro-fused pyrrolo[3,4-a]pyrrolizine and tryptanthrin framework have been synthesized and studied as potential antitumor agents. Cytotoxicity of products was screened against human erythroleukemia (K562) and human cervical carcinoma (HeLa) cell lines. Among the screened compounds. 4a, 4b and 5a were active against human erythroleukemia (K562) cell line, while 4a and 5a were active against cervical carcinoma (HeLa) cell line. In agreement with the DNA cytometry studies, the tested compounds have achieved significant cell-cycle perturbation with higher accumulation of cells in G2/M phase and induced apoptosis. Using confocal microscopy, we found that with 4a and 5a treatment of HeLa cells, actin filaments disappeared, and granular actin was distributed diffusely in the cytoplasm in 76–91% of cells. We discovered that HeLa cells after treatment with compounds 4a and 5a significantly reduced the number of cells with filopodium-like membrane protrusions (from 63 % in control cells to 29% after treatment) and a decrease in cell motility. [ABSTRACT FROM AUTHOR]